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Cell Migration

Xavier Trepat, Zaozao Chen, Ken Jacobson

10.1002/cphy.c110012

Source: Volume 2, Issue 4, October 2012

Published online: October 2012

Full Article on Wiley Online Library



Abstract

Cell migration is fundamental to establishing and maintaining the proper organization of multicellular organisms. Morphogenesis can be viewed as a consequence, in part, of cell locomotion, from large‐scale migrations of epithelial sheets during gastrulation, to the movement of individual cells during development of the nervous system. In an adult organism, cell migration is essential for proper immune response, wound repair, and tissue homeostasis, while aberrant cell migration is found in various pathologies. Indeed, as our knowledge of migration increases, we can look forward to, for example, abating the spread of highly malignant cancer cells, retarding the invasion of white cells in the inflammatory process, or enhancing the healing of wounds. This article is organized in two main sections. The first section is devoted to the single‐cell migrating in isolation such as occurs when leukocytes migrate during the immune response or when fibroblasts squeeze through connective tissue. The second section is devoted to cells collectively migrating as part of multicellular clusters or sheets. This second type of migration is prevalent in development, wound healing, and in some forms of cancer metastasis. © 2012 American Physiological Society. Compr Physiol 2:2369‐2392, 2012.

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Figure 1. Figure 1.

Different types of cell migration. (A) A stationary, spread C3H10T1/2 fibroblast triple stained with DAPI (blue) for DNA, MitoTracker (red) for mitochondria, and Alexa Fluor phalloidin 94 for F‐actin. (B) Fibroblasts migrating into wound. Top: initially, a wound was made in a confluent monolayer of MDA‐MB‐231cells by scratching using a pipette tip. Bottom: after 15 h, migrating cells began to fill in the wound 120. (C) Migrating zebrafish keratocytes with large fan‐like lamellipodia. (D) An HL‐60 cell (human promyelocytic leukemia cell) migrating on a glass substrate after differentiation with dimethyl sulfoxide (DMSO) to exhibit leukocyte‐like behavior on glass substrate. (Image in 1A and 1D are courtesy of Bing Yang and Zenon Rajfur, respectively.) Scale bars in A, C, and D are 10 μm, in B is 100 um.
Figure 2. Figure 2.

Adhesion structure and function in cells. (A) An immunofluorescence image of focal adhesions (FAs) in an NIH 3T3 cell stained with antipaxillin; (B) an interference reflection microscopy (IRM) image of FAs in a similar NIH 3T3 fibroblast on a fibronectin (FN)‐coated substrate; the very dark regions (arrows) are FAs; and (C) schematic figure for the relationship between cell adhesion, cell migration, and some of the corresponding adaptor and signal proteins. Cell matrix adhesion complexes are depicted a key component in single‐cell adhesion and migration. After activation, integrins bind extracellular matrix (ECM) and provide a link to the actin cytoskeleton. Cytoplasmic adaptor proteins bind integrin cytoplasmic domains, stabilize FA, and provide scaffolding functions. Integrin activation also initiates downstream signaling. Such signaling may regulate cell adhesion turnover, internal force development, and cytoskeletal rearrangements including formation of stress fibers, lamellipodia, filopodia, and podosomes. Cell migration also involves both ECM degradation and proteolysis and adhesion complex internalization (see section on focal adhesion dynamics). Scale bars in A and B are 10 μm.
Figure 3. Figure 3.

(A) Interference reflection microscopy (IRM) image of close adhesion in migrating fish keratocytes, the adhesion pattern consists of an outer rim (r) of very close contact skirting a crescent‐shaped band of alternating very close (v) and distant contacts (d). (B) Epifluorescent image of podosomes in a human dendritic cell with F‐actin labeling. (C) A hypothetical view of close contacts in which small diameter projections attach to the substrate and serve to draw the ventral surface closer to the substrate such that it appears gray in IRM. Integrin, talin, F‐actin have been reported to be in close adhesions [in this schematic, the actin network is depicted like that in a microvillus with parallel actin bundles but it could also be in the form of a dendritic actin network (not shown)]; however, paxillin and focal adhesion kinase (FAK) are not found in initial close contacts. Scale bars are 10 μm. Image in panel A is from Lee and Jacobson 158; image in panel B is courtesy of Aaron Neumann.
Figure 4. Figure 4.

Use of elastic substrates to map tractions in migrating cells. (A) Phase image showing a fish keratocytes crawling on an elastic polyacrylamide substrate. (B) Tractions mapped on the same cell shown in A. The Dembo Boundary element method algorithm 52 was used to calculate the cell traction distribution from the bead displacement map; the units in the map are in Dynes/cm2 (1 dyne = 10−5N). (C) The Fourier‐transform traction cytometry (FTTC) algorithm 28 was used to calculate tractions for another keratocyte; the right scale of color bar represents stress in units of Pa (1 Pa = 1 N/m2). Scale bar is 10 μm. Images are courtesy of Zenon Rajfur.
Figure 5. Figure 5.

Collective cell migration in development. (A‐D) During development of the abdomen of Drosophila melanogaster a cluster of histoblasts (green arrow) grows and migrates radially outward at the expense of the surrounding larval cells. Courtesy of Enrique Martin‐Blanco and Carla Prat. (E‐F) During development of the sensory system of zebrafish, the lateral line primordium undergoes directed migration from head to tail, leaving behind rosettes (red arrows) at periodic intervals. Scale bars: 60 μm. Courtesy of Hernan Lopez‐Schier and Filipe Pinto.
Figure 6. Figure 6.

Collective cell migration in cancer. (A) Different invasion patterns in primary melanoma invading the mid‐dermis in vivo. Arrowheads indicate scattered individual cells. Collective invasion modes include solid stands (Str), nests (N) representing cross‐sectioned strands, and single cell chains (IF, “Indian files”). H&E staining. Image modified, with permission, from Friedl and Wolf 78. (B) Invasion modes in a modified skin‐fold chamber model of orthotopic invasion of human HT‐1080 fibrosarcoma cells. Patterns include lack of invasion (top, left), disseminating single cells (top, right), and diffuse or compact strand‐like collective invasion (lower panels). Bar 250 μm. (C) Frequency of invasion modes displayed in B. Adapted, with permission, from Alexander et al. 7.
Figure 7. Figure 7.

Scheme depicting the key molecules that mediate cell‐cell adhesion during collective cell migration.
Figure 8. Figure 8.

Mechanics of collective cell migration. (A) The forces exerted by the leading edge of an MDCK epithelial cell sheet migrating on top of a microneedle array are tensile. Adapted, with permission, from reference 57. (B, C, D) Patterns of force generation and transmission in an epithelial cell sheet. (B) An active leader cell generates forces at the leading edge and transmits these forces to follower cells via cell‐cell junctions. (C) Each cell within the monolayer generates its own contractile forces. Forces are balanced locally in such a way that there is no force transmission through cell‐cell junctions. (D) Tug‐of‐war force generation and transmission. The local tractions that each cell generates are transmitted through cell‐cell junctions to generate a global gradient of tensile stress. (E) Phase contrast image of an MDCK cell sheet advancing on top of a soft polyacrylmide gel (1.2 kPa). In this model, tractions parallel (F) and perpendicular (G) to the leading edge rule out the existence of leader/follower polarity.


Figure 1.

Different types of cell migration. (A) A stationary, spread C3H10T1/2 fibroblast triple stained with DAPI (blue) for DNA, MitoTracker (red) for mitochondria, and Alexa Fluor phalloidin 94 for F‐actin. (B) Fibroblasts migrating into wound. Top: initially, a wound was made in a confluent monolayer of MDA‐MB‐231cells by scratching using a pipette tip. Bottom: after 15 h, migrating cells began to fill in the wound 120. (C) Migrating zebrafish keratocytes with large fan‐like lamellipodia. (D) An HL‐60 cell (human promyelocytic leukemia cell) migrating on a glass substrate after differentiation with dimethyl sulfoxide (DMSO) to exhibit leukocyte‐like behavior on glass substrate. (Image in 1A and 1D are courtesy of Bing Yang and Zenon Rajfur, respectively.) Scale bars in A, C, and D are 10 μm, in B is 100 um.



Figure 2.

Adhesion structure and function in cells. (A) An immunofluorescence image of focal adhesions (FAs) in an NIH 3T3 cell stained with antipaxillin; (B) an interference reflection microscopy (IRM) image of FAs in a similar NIH 3T3 fibroblast on a fibronectin (FN)‐coated substrate; the very dark regions (arrows) are FAs; and (C) schematic figure for the relationship between cell adhesion, cell migration, and some of the corresponding adaptor and signal proteins. Cell matrix adhesion complexes are depicted a key component in single‐cell adhesion and migration. After activation, integrins bind extracellular matrix (ECM) and provide a link to the actin cytoskeleton. Cytoplasmic adaptor proteins bind integrin cytoplasmic domains, stabilize FA, and provide scaffolding functions. Integrin activation also initiates downstream signaling. Such signaling may regulate cell adhesion turnover, internal force development, and cytoskeletal rearrangements including formation of stress fibers, lamellipodia, filopodia, and podosomes. Cell migration also involves both ECM degradation and proteolysis and adhesion complex internalization (see section on focal adhesion dynamics). Scale bars in A and B are 10 μm.



Figure 3.

(A) Interference reflection microscopy (IRM) image of close adhesion in migrating fish keratocytes, the adhesion pattern consists of an outer rim (r) of very close contact skirting a crescent‐shaped band of alternating very close (v) and distant contacts (d). (B) Epifluorescent image of podosomes in a human dendritic cell with F‐actin labeling. (C) A hypothetical view of close contacts in which small diameter projections attach to the substrate and serve to draw the ventral surface closer to the substrate such that it appears gray in IRM. Integrin, talin, F‐actin have been reported to be in close adhesions [in this schematic, the actin network is depicted like that in a microvillus with parallel actin bundles but it could also be in the form of a dendritic actin network (not shown)]; however, paxillin and focal adhesion kinase (FAK) are not found in initial close contacts. Scale bars are 10 μm. Image in panel A is from Lee and Jacobson 158; image in panel B is courtesy of Aaron Neumann.



Figure 4.

Use of elastic substrates to map tractions in migrating cells. (A) Phase image showing a fish keratocytes crawling on an elastic polyacrylamide substrate. (B) Tractions mapped on the same cell shown in A. The Dembo Boundary element method algorithm 52 was used to calculate the cell traction distribution from the bead displacement map; the units in the map are in Dynes/cm2 (1 dyne = 10−5N). (C) The Fourier‐transform traction cytometry (FTTC) algorithm 28 was used to calculate tractions for another keratocyte; the right scale of color bar represents stress in units of Pa (1 Pa = 1 N/m2). Scale bar is 10 μm. Images are courtesy of Zenon Rajfur.



Figure 5.

Collective cell migration in development. (A‐D) During development of the abdomen of Drosophila melanogaster a cluster of histoblasts (green arrow) grows and migrates radially outward at the expense of the surrounding larval cells. Courtesy of Enrique Martin‐Blanco and Carla Prat. (E‐F) During development of the sensory system of zebrafish, the lateral line primordium undergoes directed migration from head to tail, leaving behind rosettes (red arrows) at periodic intervals. Scale bars: 60 μm. Courtesy of Hernan Lopez‐Schier and Filipe Pinto.



Figure 6.

Collective cell migration in cancer. (A) Different invasion patterns in primary melanoma invading the mid‐dermis in vivo. Arrowheads indicate scattered individual cells. Collective invasion modes include solid stands (Str), nests (N) representing cross‐sectioned strands, and single cell chains (IF, “Indian files”). H&E staining. Image modified, with permission, from Friedl and Wolf 78. (B) Invasion modes in a modified skin‐fold chamber model of orthotopic invasion of human HT‐1080 fibrosarcoma cells. Patterns include lack of invasion (top, left), disseminating single cells (top, right), and diffuse or compact strand‐like collective invasion (lower panels). Bar 250 μm. (C) Frequency of invasion modes displayed in B. Adapted, with permission, from Alexander et al. 7.



Figure 7.

Scheme depicting the key molecules that mediate cell‐cell adhesion during collective cell migration.



Figure 8.

Mechanics of collective cell migration. (A) The forces exerted by the leading edge of an MDCK epithelial cell sheet migrating on top of a microneedle array are tensile. Adapted, with permission, from reference 57. (B, C, D) Patterns of force generation and transmission in an epithelial cell sheet. (B) An active leader cell generates forces at the leading edge and transmits these forces to follower cells via cell‐cell junctions. (C) Each cell within the monolayer generates its own contractile forces. Forces are balanced locally in such a way that there is no force transmission through cell‐cell junctions. (D) Tug‐of‐war force generation and transmission. The local tractions that each cell generates are transmitted through cell‐cell junctions to generate a global gradient of tensile stress. (E) Phase contrast image of an MDCK cell sheet advancing on top of a soft polyacrylmide gel (1.2 kPa). In this model, tractions parallel (F) and perpendicular (G) to the leading edge rule out the existence of leader/follower polarity.

References
 1. Abe K, Takeichi M. EPLIN mediates linkage of the cadherin catenin complex to F‐actin and stabilizes the circumferential actin belt. Proc Natl Acad Sci U S A 105: 13‐19, 2008.
 2. Abercrombie M, Heaysman JE, Pegrum SM. The locomotion of fibroblasts in culture. 3. Movements of particles on the dorsal surface of the leading lamella. Exp Cell Res 62: 389‐398, 1970.
 3. Aberle H, Butz S, Stappert J, Weissig H, Kemler R, Hoschuetzky H. Assembly of the cadherin‐catenin complex in vitro with recombinant proteins. J Cell Sci 107(Pt 12): 3655‐3663, 1994.
 4. Abrams EW, Vining MS, Andrew DJ. Constructing an organ: The Drosophila salivary gland as a model for tube formation. Trends Cell Biol 13: 247‐254, 2003.
 5. Agarwal R, D'Souza T, Morin PJ. Claudin‐3 and claudin‐4 expression in ovarian epithelial cells enhances invasion and is associated with increased matrix metalloproteinase‐2 activity. Cancer Res 65: 7378‐7385, 2005.
 6. Alberts B, Wilson JH, Hunt T. Molecular Biology of the Cell. New York: Garland Science, 2008.
 7. Alexander S, Koehl GE, Hirschberg M, Geissler EK, Friedl P. Dynamic imaging of cancer growth and invasion: A modified skin‐fold chamber model. Histochem Cell Biol 130: 1147‐1154, 2008.
 8. Aman A, Piotrowski T. Wnt/beta‐catenin and Fgf signaling control collective cell migration by restricting chemokine receptor expression. Dev Cell 15: 749‐761, 2008.
 9. Amatangelo MD, Bassi DE, Klein‐Szanto AJ, Cukierman E. Stroma‐derived three‐dimensional matrices are necessary and sufficient to promote desmoplastic differentiation of normal fibroblasts. Am J Pathol 167: 475‐488, 2005.
 10. Anderson JM, Van Itallie CM, Fanning AS. Setting up a selective barrier at the apical junction complex. Curr Opin Cell Biol 16: 140‐145, 2004.
 11. Anderson KI, Cross R. Contact dynamics during keratocyte motility. Curr Biol 10: 253‐260, 2000.
 12. Angelini TE, Hannezo E, Trepat X, Fredberg JJ, Weitz DA. Cell migration driven by cooperative substrate deformation patterns. Phys Rev Lett 104: 168104, 2010.
 13. Balaban NQ, Schwarz US, Riveline D, Goichberg P, Tzur G, Sabanay I, Mahalu D, Safran S, Bershadsky A, Addadi L, Geiger B. Force and focal adhesion assembly: A close relationship studied using elastic micropatterned substrates. Nat Cell Biol 3: 466‐472, 2001.
 14. Balda MS, Matter K. Tight junctions at a glance. J Cell Sci 121: 3677‐3682, 2008.
 15. Barczyk M, Carracedo S, Gullberg D. Integrins. Cell Tissue Res 339: 269‐280, 2010.
 16. Baruzzi A, Iacobucci I, Soverini S, Lowell CA, Martinelli G, Berton G. c‐Abl and Src‐family kinases cross‐talk in regulation of myeloid cell migration. FEBS Lett 584: 15‐21, 2010.
 17. Bauer R, Lehmann C, Fuss B, Eckardt F, Hoch M. The Drosophila gap junction channel gene innexin 2 controls foregut development in response to Wingless signalling. J Cell Sci 115: 1859‐1867, 2002.
 18. Beningo KA, Dembo M, Kaverina I, Small JV, Wang YL. Nascent focal adhesions are responsible for the generation of strong propulsive forces in migrating fibroblasts. J Cell Biol 153: 881‐888, 2001.
 19. Bianco A, Poukkula M, Cliffe A, Mathieu J, Luque CM, Fulga TA, Rorth P. Two distinct modes of guidance signalling during collective migration of border cells. Nature 448: 362‐365, 2007.
 20. Bindschadler M, McGrath JL. Sheet migration by wounded monolayers as an emergent property of single‐cell dynamics. J Cell Sci 120: 876‐884, 2007.
 21. Boldajipour B, Mahabaleshwar H, Kardash E, Reichman‐Fried M, Blaser H, Minina S, Wilson D, Xu Q, Raz E. Control of chemokine‐guided cell migration by ligand sequestration. Cell 132: 463‐473, 2008.
 22. Brass LF. Thrombin and platelet activation. Chest 124: 18S‐25S, 2003.
 23. Brennan K, Offiah G, McSherry EA, Hopkins AM. Tight junctions: A barrier to the initiation and progression of breast cancer? J Biomed Biotechnol 2010: 460607, 2010.
 24. Broussard JA, Webb DJ, Kaverina I. Asymmetric focal adhesion disassembly in motile cells. Curr Opin Cell Biol 20: 85‐90, 2008.
 25. Buccione R, Orth JD, McNiven MA. Foot and mouth: Podosomes, invadopodia and circular dorsal ruffles. Nat Rev Mol Cell Biol 5: 647‐657, 2004.
 26. Buechner M. Tubes and the single C. elegans excretory cell. Trends Cell Biol 12: 479‐484, 2002.
 27. Burridge K, Connell L. A new protein of adhesion plaques and ruffling membranes. J Cell Biol 97: 359‐367, 1983.
 28. Butler JP, Tolic‐Norrelykke IM, Fabry B, Fredberg JJ. Traction fields, moments, and strain energy that cells exert on their surroundings. Am J Physiol Cell Physiol 282: C595‐C605, 2002.
 29. Cai AQ, Landman KA, Hughes BD. Multi‐scale modeling of a wound‐healing cell migration assay. J Theor Biol 245: 576‐594, 2007.
 30. Carmeliet P, Tessier‐Lavigne M. Common mechanisms of nerve and blood vessel wiring. Nature 436: 193‐200, 2005.
 31. Carr I. Experimental lymphatic metastasis. J Microsc 131: 211‐220, 1983.
 32. Carragher NO, Levkau B, Ross R, Raines EW. Degraded collagen fragments promote rapid disassembly of smooth muscle focal adhesions that correlates with cleavage of pp125(FAK), paxillin, and talin. J Cell Biol 147: 619‐630, 1999.
 33. Caswell PT, Vadrevu S, Norman JC. Integrins: Masters and slaves of endocytic transport. Nat Rev Mol Cell Biol 10: 843‐853, 2009.
 34. Cavey M, Lecuit T. Molecular bases of cell‐cell junctions stability and dynamics. Cold Spring Harb Perspect Biol 1: a002998, 2009.
 35. Coles EG, Taneyhill LA, Bronner‐Fraser M. A critical role for Cadherin6B in regulating avian neural crest emigration. Dev Biol 312: 533‐544, 2007.
 36. Coraux C, Roux J, Jolly T, Birembaut P. Epithelial cell‐extracellular matrix interactions and stem cells in airway epithelial regeneration. Proc Am Thor Soc 5: 689‐694, 2008.
 37. Cronier L, Crespin S, Strale PO, Defamie N, Mesnil M. Gap junctions and cancer: New functions for an old story. Antioxid Redox Signal 11: 323‐338, 2009.
 38. Cukierman E, Pankov R, Stevens DR, Yamada KM. Taking cell‐matrix adhesions to the third dimension. Science 294: 1708‐1712, 2001.
 39. Chan CE, Odde DJ. Traction dynamics of filopodia on compliant substrates. Science 322: 1687‐1691, 2008.
 40. Chaplain MA, McDougall SR, Anderson AR. Mathematical modeling of tumor‐induced angiogenesis. Ann Rev Biomed Eng 8: 233‐257, 2006.
 41. Chen W‐T. Induction of spreading during fibroblast movement. J Cell Biol 81: 684‐691, 1979.
 42. Chen WT, Wang JY. Specialized surface protrusions of invasive cells, invadopodia and lamellipodia, have differential MT1‐MMP, MMP‐2, and TIMP‐2 localization. Ann N Y Acad Sci 878: 361‐371, 1999.
 43. Chen X, Gumbiner BM. Paraxial protocadherin mediates cell sorting and tissue morphogenesis by regulating C‐cadherin adhesion activity. J Cell Biol 174: 301‐313, 2006.
 44. Choi CK, Vicente‐Manzanares M, Zareno J, Whitmore LA, Mogilner A, Horwitz AR. Actin and alpha‐actinin orchestrate the assembly and maturation of nascent adhesions in a myosin II motor‐independent manner. Nat Cell Biol 10: 1039‐1050, 2008.
 45. Christiansen JJ, Rajasekaran AK. Reassessing epithelial to mesenchymal transition as a prerequisite for carcinoma invasion and metastasis. Cancer Res 66: 8319‐8326, 2006.
 46. Dale PD, Maini PK, Sherratt JA. Mathematical modeling of corneal epithelial wound healing. Math Biosci 124: 127‐147, 1994.
 47. Damm EW, Winklbauer R. PDGF‐A controls mesoderm cell orientation and radial intercalation during Xenopus gastrulation. Development 138: 565‐575, 2011.
 48. David NB, Sapede D, Saint‐Etienne L, Thisse C, Thisse B, Dambly‐Chaudiere C, Rosa FM, Ghysen A. Molecular basis of cell migration in the fish lateral line: Role of the chemokine receptor CXCR4 and of its ligand, SDF1. Proc Natl Acad Sci U S A 99: 16297‐16302, 2002.
 49. Davies JA. Watching tubules glow and branch. Curr Opin Genet Dev 15: 364‐370, 2005.
 50. de Beus E, Jacobson K. Integrin involvement in keratocyte locomotion. Cell Motil Cytoskeleton 41: 126‐137, 1998.
 51. del Pozo MA, Balasubramanian N, Alderson NB, Kiosses WB, Grande‐Garcia A, Anderson RG, Schwartz MA. Phospho‐caveolin‐1 mediates integrin‐regulated membrane domain internalization. Nat Cell Biol 7: 901‐908, 2005.
 52. Dembo M, Oliver T, Jacobson K. Imaging the traction stresses exerted by locomoting cells with the elastic substratum method. Biophys J 70: 2008‐2022, 1996.
 53. Dembo M, Wang Y‐L. Stresses at the cell‐to‐substrate interface during locomotion of fibroblasts. Biophys J 76: 2307‐2316, 1999.
 54. Digman MA, Gratton E. Analysis of diffusion and binding in cells using the RICS approach. Microsc Res Tech 72: 323‐332, 2009.
 55. Digman MA, Wiseman PW, Choi C, Horwitz AR, Gratton E. Stoichiometry of molecular complexes at adhesions in living cells. Proc Natl Acad Sci U S A 106: 2170‐2175, 2009.
 56. Drees F, Pokutta S, Yamada S, Nelson WJ, Weis WI. Alpha‐catenin is a molecular switch that binds E‐cadherin‐beta‐catenin and regulates actin‐filament assembly. Cell 123: 903‐915, 2005.
 57. du Roure O, Saez A, Buguin A, Austin RH, Chavrier P, Siberzan P, Ladoux B. Force mapping in epithelial cell migration. Proc Natl Acad Sci U S A 102: 2390‐2395, 2005.
 58. Duchek P, Rorth P. Guidance of cell migration by EGF receptor signaling during Drosophila oogenesis. Science 291: 131‐133, 2001.
 59. Duchek P, Somogyi K, Jekely G, Beccari S, Rorth P. Guidance of cell migration by the Drosophila PDGF/VEGF receptor. Cell 107: 17‐26, 2001.
 60. Dunn GA. Mechanisms of fibroblast locomotion. In: Curtis, ASG and Pitts, JD, editor Cell Adhesion and Motility. 3rd Symposium of the British Society for Cell Biology. Cambridge: Cambridge University Press, 1980, p. 409‐423.
 61. Ebnet K, Suzuki A, Ohno S, Vestweber D. Junctional adhesion molecules (JAMs): More molecules with dual functions? J Cell Sci 117: 19‐29, 2004.
 62. Edwards DC, Sanders LC, Bokoch GM, Gill GN. Activation of LIM‐kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol 1: 253‐259, 1999.
 63. Eghbali B, Kessler JA, Reid LM, Roy C, Spray DC. Involvement of gap junctions in tumorigenesis: Transfection of tumor cells with connexin 32 cDNA retards growth in vivo. Proc Natl Acad Sci U S A 88: 10701‐10705, 1991.
 64. Emsley J, Knight CG, Farndale RW, Barnes MJ, Liddington RC. Structural basis of collagen recognition by integrin alpha2beta1. Cell 101: 47‐56, 2000.
 65. Etienne‐Manneville S, Hall A. Integrin‐mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 106: 489‐498, 2001.
 66. Even‐Ram S, Doyle AD, Conti MA, Matsumoto K, Adelstein RS, Yamada KM. Myosin IIA regulates cell motility and actomyosin‐microtubule crosstalk. Nat Cell Biol 9: 299‐309, 2007.
 67. Even‐Ram S, Yamada KM. Cell migration in 3D matrix. Curr Opin Cell Biol 17: 524‐532, 2005.
 68. Ewald AJ, Brenot A, Duong M, Chan BS, Werb Z. Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. Dev Cell 14: 570‐581, 2008.
 69. Ezratty EJ, Bertaux C, Marcantonio EE, Gundersen GG. Clathrin mediates integrin endocytosis for focal adhesion disassembly in migrating cells. J Cell Biol 187: 733‐747, 2009.
 70. Ezratty EJ, Partridge MA, Gundersen GG. Microtubule‐induced focal adhesion disassembly is mediated by dynamin and focal adhesion kinase. Nat Cell Biol 7: 581‐590, 2005.
 71. Farooqui R, Fenteany G. Multiple rows of cells behind an epithelial wound edge extend cryptic lamellipodia to collectively drive cell‐sheet movement. J Cell Sci 118: 51‐63, 2005.
 72. Feramisco JR, Smart JE, Burridge K, Helfman DM, Thomas GP. Co‐existence of vinculin and a vinculin‐like protein of higher molecular weight in smooth muscle. J Biol Chem 257: 11024‐11031, 1982.
 73. Fournier MF, Sauser R, Ambrosi D, Meister JJ, Verkhovsky AB. Force transmission in migrating cells. J Cell Biol 188: 287‐297, 2010.
 74. Franke JD, Montague RA, Kiehart DP. Nonmuscle myosin II generates forces that transmit tension and drive contraction in multiple tissues during dorsal closure. Curr Biol 15: 2208‐2221, 2005.
 75. Friedl P, Gilmour D. Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol 10: 445‐457, 2009.
 76. Friedl P, Noble PB, Walton PA, Laird DW, Chauvin PJ, Tabah RJ, Black M, Zanker KS. Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. Cancer Res 55: 4557‐4560, 1995.
 77. Friedl P, Wolf K. Tumour‐cell invasion and migration: Diversity and escape mechanisms. Nat Rev Cancer 3: 362‐374, 2003.
 78. Friedl P, Wolf K. Tube travel: The role of proteases in individual and collective cancer cell invasion. Cancer Res 68: 7247‐7249, 2008.
 79. Friedl P, Wolf K. Plasticity of cell migration: A multiscale tuning model. J Cell Biol 188: 11‐19, 2010.
 80. Fujita Y, Krause G, Scheffner M, Zechner D, Leddy HE, Behrens J, Sommer T, Birchmeier W. Hakai, a c‐Cbl‐like protein, ubiquitinates and induces endocytosis of the E‐cadherin complex. Nat Cell Biol 4: 222‐231, 2002.
 81. Furuse M, Hirase T, Itoh M, Nagafuchi A, Yonemura S, Tsukita S, Tsukita S. Occludin: A novel integral membrane protein localizing at tight junctions. J Cell Biol 123: 1777‐1788, 1993.
 82. Furuse M, Tsukita S. Claudins in occluding junctions of humans and flies. Trends Cell Biol 16: 181‐188, 2006.
 83. Gaggioli C. Collective invasion of carcinoma cells: When the fibroblasts take the lead. Cell Adh Migr 2: 45‐47, 2008.
 84. Gaggioli C, Hooper S, Hidalgo‐Carcedo C, Grosse R, Marshall JF, Harrington K, Sahai E. Fibroblast‐led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol 9: 1392‐1400, 2007.
 85. Galbraith CG, Sheetz MP. A micromachined device provides a new bend on fibroblast traction forces. Proc Natl Acad Sci U S A 94: 9114‐9118, 1997.
 86. Galbraith CG, Sheetz MP. Keratocytes pull with similar forces on their dorsal and ventral surfaces. J Cell Biol 147: 1313‐1324, 1999.
 87. Galbraith CG, Yamada KM, Sheetz MP. The relationship between force and focal complex development. J Cell Biol 159: 695‐705, 2002.
 88. Gardel ML, Sabass B, Ji L, Danuser G, Schwarz US, Waterman CM. Traction stress in focal adhesions correlates biphasically with actin retrograde flow speed. J Cell Biol 183: 999‐1005, 2008.
 89. Garrod D, Chidgey M. Desmosome structure, composition and function. Biochim Biophys Acta 1778: 572‐587, 2008.
 90. Garrod DR, Berika MY, Bardsley WF, Holmes D, Tabernero L. Hyper‐adhesion in desmosomes: Its regulation in wound healing and possible relationship to cadherin crystal structure. J Cell Sci 118: 5743‐5754, 2005.
 91. Geiger B, Bershadsky A, Pankov R, Yamada KM. Transmembrane crosstalk between the extracellular matrix–cytoskeleton crosstalk. Nat Rev Mol Cell Biol 2: 793‐805, 2001.
 92. Geiger B, Spatz JP, Bershadsky AD. Environmental sensing through focal adhesions. Nat Rev Mol Cell Biol 10: 21‐33, 2009.
 93. Gerhardt H, Golding M, Fruttiger M, Ruhrberg C, Lundkvist A, Abramsson A, Jeltsch M, Mitchell C, Alitalo K, Shima D, Betsholtz C. VEGF guides angiogenic sprouting utilizing endothelial tip cell filopodia. J Cell Biol 161: 1163‐1177, 2003.
 94. Getsios S, Huen AC, Green KJ. Working out the strength and flexibility of desmosomes. Nat Rev Mol Cell Biol 5: 271‐281, 2004.
 95. Ghysen A, Dambly‐Chaudiere C. The lateral line microcosmos. Genes Dev 21: 2118‐2130, 2007.
 96. Giampieri S, Manning C, Hooper S, Jones L, Hill CS, Sahai E. Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility. Nat Cell Biol 11: 1287‐1296, 2009.
 97. Gimona M, Buccione R, Courtneidge SA, Linder S. Assembly and biological role of podosomes and invadopodia. Curr Opin Cell Biol 20: 235‐241, 2008.
 98. Glazier JA, Graner F. Simulation of the differential adhesion driven rearrangement of biological cells. Phys Rev E Stat Phys Plasmas Fluids Relat Interdiscip Topics 47: 2128‐2154, 1993.
 99. Gligorijevic B, Condeelis J. Stretching the timescale of intravital imaging in tumors. Cell Adh Migr 3: 313‐315, 2009.
 100. Goliger JA, Paul DL. Wounding alters epidermal connexin expression and gap junction‐mediated intercellular communication. Mol Biol Cell 6: 1491‐1501, 1995.
 101. Goodrich HB. Cell behaviour in tissue cultures. Biol Bull: 252‐262., 1924.
 102. Grande‐Garcia A, Echarri A, de Rooij J, Alderson NB, Waterman‐Storer CM, Valdivielso JM, del Pozo MA. Caveolin‐1 regulates cell polarization and directional migration through Src kinase and Rho GTPases. J Cell Biol 177: 683‐694, 2007.
 103. Graner F, Glazier JA. Simulation of biological cell sorting using a two‐dimensional extended Potts model. Phys Rev Lett 69: 2013‐2016, 1992.
 104. Gumbiner BM. Regulation of cadherin‐mediated adhesion in morphogenesis. Nat Rev Mol Cell Biol 6: 622‐634, 2005.
 105. Gupton SL, Waterman‐Storer CM. Spatiotemporal feedback between actomyosin and focal‐adhesion systems optimizes rapid cell migration. Cell 125: 1361‐1374, 2006.
 106. Gurtner GC, Werner S, Barrandon Y, Longaker MT. Wound repair and regeneration. Nature 453: 314‐321, 2008.
 107. Haas P, Gilmour D. Chemokine Signaling Mediates Self‐Organizing Tissue Migration in the Zebrafish Lateral Line: Elsevier, 2006, pp. 673‐680.
 108. Hall A. Rho GTPases and the actin cytoskeleton. Science 279: 509‐514, 1998.
 109. Harris A, Wild P, Stopak D. Silicone rubber substrata: A new wrinkle in the study of cell locomotion. Science 208: 177‐179, 1980.
 110. Hartsock A, Nelson WJ. Adherens and tight junctions: Structure, function and connections to the actin cytoskeleton. Biochim Biophys Acta 1778: 660‐669, 2008.
 111. Hava D, Forster U, Matsuda M, Cui S, Link BA, Eichhorst J, Wiesner B, Chitnis A, Abdelilah‐Seyfried S. Apical membrane maturation and cellular rosette formation during morphogenesis of the zebrafish lateral line. J Cell Sci 122: 687‐695, 2009.
 112. Heath JP, Peachey LD. Morphology of fibroblasts in collagen gels: A study using 400 keV electron microscopy and computer graphics. Cell Motil Cytoskeleton 14: 382‐392, 1989.
 113. Hellstrom M, Phng LK, Hofmann JJ, Wallgard E, Coultas L, Lindblom P, Alva J, Nilsson AK, Karlsson L, Gaiano N, Yoon K, Rossant J, Iruela‐Arispe ML, Kalen M, Gerhardt H, Betsholtz C. Dll4 signalling through Notch1 regulates formation of tip cells during angiogenesis. Nature 445: 776‐780, 2007.
 114. Hernandez SE, Krishnaswami M, Miller AL, Koleske AJ. How do Abl family kinases regulate cell shape and movement? Trends Cell Biol 14: 36‐44, 2004.
 115. Hertle MD, Kubler MD, Leigh IM, Watt FM. Aberrant integrin expression during epidermal wound healing and in psoriatic epidermis. J Clin Invest 89: 1892‐1901, 1992.
 116. Holmes SJ. The behavior of the epidermis of amphibians when cultivated outside the body. J Exp Zool 17: 281‐295, 1914.
 117. Hu H, Marton TF, Goodman CS. Plexin B mediates axon guidance in Drosophila by simultaneously inhibiting active Rac and enhancing RhoA signaling. Neuron 32: 39‐51, 2001.
 118. Huang C. Roles of E3 ubiquitin ligases in cell adhesion and migration. Cell Adh Migr 4: 10‐18, 2010.
 119. Huang C, Jacobson K, Schaller MD. A role for JNK‐paxillin signaling in cell migration. Cell Cycle 3: 4‐6, 2004.
 120. Huang C, Rajfur Z, Borchers C, Schaller MD, Jacobson K. JNK phosphorylates paxillin and regulates cell migration. Nature 424: 219‐223, 2003.
 121. Huang C, Rajfur Z, Yousefi N, Chen Z, Jacobson K, Ginsberg MH. Talin phosphorylation by Cdk5 regulates Smurf1‐mediated talin head ubiquitylation and cell migration. Nat Cell Biol 11: 624‐630, 2009.
 122. Huang RP, Fan Y, Hossain MZ, Peng A, Zeng ZL, Boynton AL. Reversion of the neoplastic phenotype of human glioblastoma cells by connexin 43 (cx43). Cancer Res 58: 5089‐5096, 1998.
 123. Hulpiau P, van Roy F. Molecular evolution of the cadherin superfamily. Int J Biochem Cell Biol 41: 349‐369, 2009.
 124. Humphries MJ. Integrin structure. Biochem Soc Trans 28: 311‐339, 2000.
 125. Hutson MS, Tokutake Y, Chang MS, Bloor JW, Venakides S, Kiehart DP, Edwards GS. Forces for morphogenesis investigated with laser microsurgery and quantitative modeling. Science 300: 145‐149, 2003.
 126. Huttenlocher A, Palecek SP, Lu Q, Zhang W, Mellgren RL, Lauffenburger DA, Ginsberg MH, Horwitz AF. Regulation of cell migration by the calcium‐dependent protease calpain. J Biol Chem 272: 32719‐32722, 1997.
 127. Huveneers S, Danen EH. Adhesion signaling ‐ crosstalk between integrins, Src and Rho. J Cell Sci 122: 1059‐1069, 2009.
 128. Hynes RO, Lander AD. Contact and adhesive specificities in the associations, migrations, and targeting of cells and axons. Cell 68: 303‐322, 1992.
 129. Ikenouchi J, Furuse M, Furuse K, Sasaki H, Tsukita S, Tsukita S. Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. J Cell Biol 171: 939‐945, 2005.
 130. Ilic D, Furuta Y, Kanazawa S, Takeda N, Sobue K, Nakatsuji N, Nomura S, Fujimoto J, Okada M, Yamamoto T. Reduced cell motility and enhanced focal adhesion contact formation in cells from FAK‐deficient mice. Nature 377: 539‐544, 1995.
 131. Ito A, Koma Y, Uchino K, Okada T, Ohbayashi C, Tsubota N, Okada M. Increased expression of connexin 26 in the invasive component of lung squamous cell carcinoma: Significant correlation with poor prognosis. Cancer Lett 234: 239‐248, 2006.
 132. Izzard CS, Lochner LR. Cell‐to‐substrate contacts in living fibroblasts: An interference reflexion study with an evaluation of the technique. J Cell Sci 21: 129‐159, 1976.
 133. Jacinto A, Wood W, Balayo T, Turmaine M, Martinez‐Arias A, Martin P. Dynamic actin‐based epithelial adhesion and cell matching during Drosophila dorsal closure. Curr Biol 10: 1420‐1426, 2000.
 134. Jain RK, Munn LL, Fukumura D. Dissecting tumour pathophysiology using intravital microscopy. Nat Rev Cancer 2: 266‐276, 2002.
 135. Jung AC, Ribeiro C, Michaut L, Certa U, Affolter M. Polychaetoid/ZO‐1 is required for cell specification and rearrangement during Drosophila tracheal morphogenesis. Curr Biol 16: 1224‐1231, 2006.
 136. Jurado C, Haserick JR, Lee J. Slipping or gripping? Fluorescent speckle microscopy in fish keratocytes reveals two different mechanisms for generating a retrograde flow of actin. Mol Biol Cell 16: 507‐518, 2005.
 137. Kalra J, Shao Q, Qin H, Thomas T, Alaoui‐Jamali MA, Laird DW. Cx26 inhibits breast MDA‐MB‐435 cell tumorigenic properties by a gap junctional intercellular communication‐independent mechanism. Carcinogenesis 27: 2528‐2537, 2006.
 138. Kalluri R, Weinberg RA. The basics of epithelial‐mesenchymal transition. J Clin Invest 119: 1420‐1428, 2009.
 139. Kanchanawong P, Shtengel G, Pasapera AM, Ramko EB, Davidson MW, Hess HF, Waterman CM. Nanoscale architecture of integrin‐based cell adhesions. Nature 468: 580‐584, 2010.
 140. Kaverina I, Krylyshkina O, Small JV. Microtubule targeting of substrate contacts promotes their relaxation and dissociation. J Cell Biol 146: 1033‐1044, 1999.
 141. Kawakami T, Nabeshima K, Hamasaki M, Iwasaki A, Shirakusa T, Iwasaki H. Small cluster invasion: A possible link between micropapillary pattern and lymph node metastasis in pT1 lung adenocarcinomas. Virchows Arch 454: 61‐70, 2009.
 142. Keren K, Yam PT, Kinkhabwala A, Mogilner A, Theriot JA. Intracellular fluid flow in rapidly moving cells. Nat Cell Biol 11: 1219‐1224, 2009.
 143. Khan K, Hardy R, Haq A, Ogunbiyi O, Morton D, Chidgey M. Desmocollin switching in colorectal cancer. Br J Cancer 95: 1367‐1370, 2006.
 144. Kiehart DP, Galbraith CG, Edwards KA, Rickoll WL, Montague RA. Multiple forces contribute to cell sheet morphogenesis for dorsal closure in Drosophila. J Cell Biol 149: 471‐490, 2000.
 145. Kim M, Carman CV, Springer TA. Bidirectional transmembrane signaling by cytoplasmic domain separation in integrins. Science 301: 1720‐1725, 2003.
 146. Kobayashi H, Aiba S, Yoshino Y, Tagami H. Acute cutaneous barrier disruption activates epidermal p44/42 and p38 mitogen‐activated protein kinases in human and hairless guinea pig skin. Exp Dermatol 12: 734‐746, 2003.
 147. Kobielak A, Pasolli HA, Fuchs E. Mammalian formin‐1 participates in adherens junctions and polymerization of linear actin cables. Nat Cell Biol 6: 21‐30, 2004.
 148. Kole TP, Tseng Y, Jiang I, Katz JL, Wirtz D. Intracellular mechanics of migrating fibroblasts. Mol Biol Cell 16: 328‐338, 2005.
 149. Krause M, Dent EW, Bear JE, Loureiro JJ, Gertler FB. Ena/VASP proteins: Regulators of the actin cytoskeleton and cell migration. Annu Rev Cell Dev Biol 19: 541‐564, 2003.
 150. Krylyshkina O, Anderson KI, Kaverina I, Upmann I, Manstein DJ, Small JV, Toomre DK. Nanometer targeting of microtubules to focal adhesions. J Cell Biol 161: 853‐859, 2003.
 151. Lammermann T, Bader BL, Monkley SJ, Worbs T, Wedlich‐Soldner R, Hirsch K, Keller M, Forster R, Critchley DR, Fassler R, Sixt M. Rapid leukocyte migration by integrin‐independent flowing and squeezing. Nature 453: 51‐55, 2008.
 152. Langbein L, Pape UF, Grund C, Kuhn C, Praetzel S, Moll I, Moll R, Franke WW. Tight junction‐related structures in the absence of a lumen: Occludin, claudins and tight junction plaque proteins in densely packed cell formations of stratified epithelia and squamous cell carcinomas. Eur J Cell Biol 82: 385‐400, 2003.
 153. Larrivee B, Freitas C, Suchting S, Brunet I, Eichmann A. Guidance of vascular development: Lessons from the nervous system. Circ Res 104: 428‐441, 2009.
 154. Laudanna C, Campbell JJ, Butcher EC. Role of Rho in chemoattractant‐activated leukocyte adhesion through integrins. Science 271: 981‐983, 1996.
 155. Laukaitis CM, Webb DJ, Donais K, Horwitz AF. Differential dynamics of alpha 5 integrin, paxillin, and alpha‐actinin during formation and disassembly of adhesions in migrating cells. J Cell Biol 153: 1427‐1440, 2001.
 156. Lecaudey V, Cakan‐Akdogan G, Norton WH, Gilmour D. Dynamic Fgf signaling couples morphogenesis and migration in the zebrafish lateral line primordium. Development 135: 2695‐2705, 2008.
 157. Lee J, Ishihara A, Theriot JA, Jacobson K. Principles of locomotion for simple‐shaped cells. Nature 362: 167‐171, 1993.
 158. Lee J, Jacobson K. The composition and dynamics of cell‐substratum adhesions in locomoting fish keratocytes. J Cell Sci 110(Pt 22): 2833‐2844, 1997.
 159. Lee J, Leonard M, Oliver T, Ishihara A, Jacobson K. Traction forces generated by locomoting keratocytes. J Cell Biol 127: 1957‐1964, 1994.
 160. Linder S. The matrix corroded: Podosomes and invadopodia in extracellular matrix degradation. Trends Cell Biol 17: 107‐117, 2007.
 161. Linder S, Nelson D, Weiss M, Aepfelbacher M. Wiskott‐Aldrich syndrome protein regulates podosomes in primary human macrophages. Proc Natl Acad Sci U S A 96: 9648‐9653, 1999.
 162. Liotta LA, Saidel MG, Kleinerman J. The significance of hematogenous tumor cell clumps in the metastatic process. Cancer Res 36: 889‐894, 1976.
 163. Liotta LA, Steeg PS, Stetler‐Stevenson WG. Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 64: 327‐336, 1991.
 164. Liu Z, Tan JL, Cohen DM, Yang MT, Sniadecki NJ, Ruiz SA, Nelson CM, Chen CS. Mechanical tugging force regulates the size of cell‐cell junctions. Proc Natl Acad Sci U S A 107: 9944‐9949, 2010.
 165. Lo CM, Wang HB, Dembo M, Wang YL. Cell movement is guided by the rigidity of the substrate. Biophys J 79: 144‐152, 2000.
 166. Lo SH, Chen LB. Focal adhesion as a signal transduction organelle. Cancer Metastasis Rev 13: 9‐24, 1994.
 167. Lo SH, Janmey PA, Hartwig JH, Chen LB. Interactions of tensin with actin and identification of its three distinct actin‐binding domains. J Cell Biol 125: 1067‐1075, 1994.
 168. Lu P, Werb Z. Patterning mechanisms of branched organs. Science 322: 1506‐1509, 2008.
 169. Llense F, Martin‐Blanco E. JNK signaling controls border cell cluster integrity and collective cell migration. Curr Biol 18: 538‐544, 2008.
 170. Ma X, Lynch HE, Scully PC, Hutson MS. Probing embryonic tissue mechanics with laser hole drilling. Phys Biol 6: 036004, 2009.
 171. Macpherson IR, Hooper S, Serrels A, McGarry L, Ozanne BW, Harrington K, Frame MC, Sahai E, Brunton VG. p120‐catenin is required for the collective invasion of squamous cell carcinoma cells via a phosphorylation‐independent mechanism. Oncogene 26: 5214‐5228, 2007.
 172. Machacek M, Hodgson L, Welch C, Elliott H, Pertz O, Nalbant P, Abell A, Johnson GL, Hahn KM, Danuser G. Coordination of Rho GTPase activities during cell protrusion. Nature 461: 99‐103, 2009.
 173. Mantzaris NV, Webb S, Othmer HG. Mathematical modeling of tumor‐induced angiogenesis. J Math Biol 49: 111‐187, 2004.
 174. Mark S, Shlomovitz R, Gov NS, Poujade M, Grasland‐Mongrain E, Silberzan P. Physical model of the dynamic instability in an expanding cell culture. Biophys J 98: 361‐370, 2010.
 175. Martin P. Wound healing–aiming for perfect skin regeneration. Science 276: 75‐81, 1997.
 176. Martin P, Parkhurst SM. Parallels between tissue repair and embryo morphogenesis. Development 131: 3021‐3034, 2004.
 177. Maruthamuthu V, Aratyn‐Schaus Y, Gardel ML. Conserved F‐actin dynamics and force transmission at cell adhesions. Curr Opin Cell Biol 22: 583‐588, 2010.
 178. McLachlan E, Shao Q, Wang HL, Langlois S, Laird DW. Connexins act as tumor suppressors in three‐dimensional mammary cell organoids by regulating differentiation and angiogenesis. Cancer Res 66: 9886‐9894, 2006.
 179. McMahon A, Supatto W, Fraser SE, Stathopoulos A. Dynamic analyses of drosophila gastrulation provide insights into collective cell migration. Science 322: 1546‐1550, 2008.
 180. Mese G, Richard G, White TW. Gap junctions: Basic structure and function. J Invest Dermatol 127: 2516‐2524, 2007.
 181. Mitra SK, Hanson DA, Schlaepfer DD. Focal adhesion kinase: In command and control of cell motility. Nat Rev Mol Cell Biol 6: 56‐68, 2005.
 182. Mogilner A, Oster G. Cell motility driven by actin polymerization. Biophys J 71: 3030‐3045, 1996.
 183. Mogilner A, Oster G. Force generation by actin polymerization II: The elastic ratchet and tethered filaments. Biophys J 84: 1591‐1605, 2003.
 184. Momiyama M, Omori Y, Ishizaki Y, Nishikawa Y, Tokairin T, Ogawa J, Enomoto K. Connexin26‐mediated gap junctional communication reverses the malignant phenotype of MCF‐7 breast cancer cells. Cancer Sci 94: 501‐507, 2003.
 185. Nabeshima K, Inoue T, Shimao Y, Kataoka H, Koono M. Cohort migration of carcinoma cells: Differentiated colorectal carcinoma cells move as coherent cell clusters or sheets. Histol Histopathol 14: 1183‐1197, 1999.
 186. Nagano T, Yoneda T, Hatanaka Y, Kubota C, Murakami F, Sato M. Filamin A‐interacting protein (FILIP) regulates cortical cell migration out of the ventricular zone. Nat Cell Biol 4: 495‐501, 2002.
 187. Nagar B, Overduin M, Ikura M, Rini JM. Structural basis of calcium‐induced E‐cadherin rigidification and dimerization. Nature 380: 360‐364, 1996.
 188. Nagel M, Tahinci E, Symes K, Winklbauer R. Guidance of mesoderm cell migration in the Xenopus gastrula requires PDGF signaling. Development 131: 2727‐2736, 2004.
 189. Nakahara H, Otani T, Sasaki T, Miura Y, Takai Y, Kogo M. Involvement of Cdc42 and Rac small G proteins in invadopodia formation of RPMI7951 cells. Genes Cells 8: 1019‐1027, 2003.
 190. Nakaya Y, Sheng G. Epithelial to mesenchymal transition during gastrulation: An embryological view. Dev Growth Differ 50: 755‐766, 2008.
 191. Nalbant P, Hodgson L, Kraynov V, Toutchkine A, Hahn KM. Activation of endogenous Cdc42 visualized in living cells. Science 305: 1615‐1619, 2004.
 192. Nechiporuk A, Raible DW. FGF‐dependent mechanosensory organ patterning in zebrafish. Science 320: 1774‐1777, 2008.
 193. Nelson WJ. Tube morphogenesis: Closure, but many openings remain. Trends Cell Biol 13: 615‐621, 2003.
 194. Niessen CM. Tight junctions/adherens junctions: Basic structure and function. J Invest Dermatol 127: 2525‐2532, 2007.
 195. Niggemann B, Drell TLt, Joseph J, Weidt C, Lang K, Zaenker KS, Entschladen F. Tumor cell locomotion: Differential dynamics of spontaneous and induced migration in a 3D collagen matrix. Exp Cell Res 298: 178‐187, 2004.
 196. Ninov N, Chiarelli DA, Martin‐Blanco E. Extrinsic and intrinsic mechanisms directing epithelial cell sheet replacement during Drosophila metamorphosis. Development 134: 367‐379, 2007.
 197. Ninov N, Menezes‐Cabral S, Prat‐Rojo C, Manjon C, Weiss A, Pyrowolakis G, Affolter M, Martin‐Blanco E. Dpp signaling directs cell motility and invasiveness during epithelial morphogenesis. Curr Biol 20: 513‐520.
 198. Nissen NN, Polverini PJ, Koch AE, Volin MV, Gamelli RL, DiPietro LA. Vascular endothelial growth factor mediates angiogenic activity during the proliferative phase of wound healing. Am J Pathol 152: 1445‐1452, 1998.
 199. Noren NK, Liu BP, Burridge K, Kreft B. p120 catenin regulates the actin cytoskeleton via Rho family GTPases. J Cell Biol 150: 567‐580, 2000.
 200. Nurden AT, Nurden P, Sanchez M, Andia I, Anitua E. Platelets and wound healing. Front Biosci 13: 3532‐3548, 2008.
 201. Nusrat A, Brown GT, Tom J, Drake A, Bui TT, Quan C, Mrsny RJ. Multiple protein interactions involving proposed extracellular loop domains of the tight junction protein occludin. Mol Biol Cell 16: 1725‐1734, 2005.
 202. Ogata S, Morokuma J, Hayata T, Kolle G, Niehrs C, Ueno N, Cho KW. TGF‐beta signaling‐mediated morphogenesis: Modulation of cell adhesion via cadherin endocytosis. Genes Dev 21: 1817‐1831, 2007.
 203. Oliver T, Dembo M, Jacobson K. Separation of propulsive and adhesive traction stresses in locomoting keratocytes. J Cell Biol 145: 589‐604, 1999.
 204. Omelchenko T, Vasiliev JM, Gelfand IM, Feder HH, Bonder EM. Rho‐dependent formation of epithelial “leader” cells during wound healing. Proc Natl Acad Sci U S A 100: 10788‐10793, 2003.
 205. Ouaknin GY, Bar‐Yoseph PZ. Stochastic collective movement of cells and fingering morphology: No maverick cells. Biophys J 97: 1811‐1821, 2009.
 206. Pankov R, Endo Y, Even‐Ram S, Araki M, Clark K, Cukierman E, Matsumoto K, Yamada KM. A Rac switch regulates random versus directionally persistent cell migration. J Cell Biol 170: 793‐802, 2005.
 207. Parsons JT. Focal adhesion kinase: The first ten years. J Cell Sci 116: 1409‐1416, 2003.
 208. Pastor‐Pareja JC, Grawe F, Martin‐Blanco E, Garcia‐Bellido A. Invasive cell behavior during Drosophila imaginal disc eversion is mediated by the JNK signaling cascade. Dev Cell 7: 387‐399, 2004.
 209. Patel SD, Ciatto C, Chen CP, Bahna F, Rajebhosale M, Arkus N, Schieren I, Jessell TM, Honig B, Price SR, Shapiro L. Type II cadherin ectodomain structures: Implications for classical cadherin specificity. Cell 124: 1255‐1268, 2006.
 210. Pelham R, Wang Y. High resolution detection of mechanical forces exerted by locomoting fibroblasts on the substrate. Mol Biol Cell 10: 933‐945, 1999.
 211. Pelham RJ, Wang Y‐L. Cell locomotion and focal adhesions are regulated by substrate flexibility. Proc Natl Acad Sci U S A 94: 13661‐13665, 1997.
 212. Pertz O, Hahn KM. Designing biosensors for Rho family proteins–deciphering the dynamics of Rho family GTPase activation in living cells. J Cell Sci 117: 1313‐1318, 2004.
 213. Pollard TD, Borisy GG. Cellular motility driven by assembly and disassembly of actin filaments. Cell 112: 453‐465, 2003.
 214. Prass M, Jacobson K, Mogilner A, Radmacher M. Direct measurement of the lamellipodial protrusive force in a migrating cell. J Cell Biol 174: 767‐772, 2006.
 215. Puck TT, Cieciura SJ, Fisher HW. Clonal growth in vitro of human cells with fibroblastic morphology; comparison of growth and genetic characteristics of single epithelioid and fibroblast‐like cells from a variety of human organs. J Exp Med 106: 145‐158, 1957.
 216. Radice GP. Locomotion and cell‐substratum contacts of Xenopus epidermal cells in vitro and in situ. J Cell Sci 44: 201‐223, 1980.
 217. Rauzi M, Verant P, Lecuit T, Lenne PF. Nature and anisotropy of cortical forces orienting Drosophila tissue morphogenesis. Nat Cell Biol 10: 1401‐1410, 2008.
 218. Redd MJ, Cooper L, Wood W, Stramer B, Martin P. Wound healing and inflammation: Embryos reveal the way to perfect repair. Philos Trans R Soc Lond B Biol Sci 359: 777‐784, 2004.
 219. Revenu C, Gilmour D. EMT 2.0: shaping epithelia through collective migration. Curr Opin Genet Dev 19: 338‐342, 2009.
 220. Reyes CD, Garcia AJ. Engineering integrin‐specific surfaces with a triple‐helical collagen‐mimetic peptide. J Biomed Mater Res A 65: 511‐523, 2003.
 221. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR. Cell migration: Integrating signals from front to back. Science 302: 1704‐1709, 2003.
 222. Rimm DL, Koslov ER, Kebriaei P, Cianci CD, Morrow JS. Alpha 1(E)‐catenin is an actin‐binding and ‐bundling protein mediating the attachment of F‐actin to the membrane adhesion complex. Proc Natl Acad Sci U S A 92: 8813‐8817, 1995.
 223. Riveline D, Zamir E, Balaban NQ, Schwarz US, Ishizaki T, Narumiya S, Kam Z, Geiger B, Bershadsky AD. Focal contacts as mechanosensors: Externally applied local mechanical force induces growth of focal contacts by an mDia1‐dependent and ROCK‐independent mechanism. J Cell Biol 153: 1175‐1186, 2001.
 224. Rorth P. Collective cell migration. Annu Rev Cell Dev Biol 25: 407‐429, 2009.
 225. Rottner K, Hall A, Small JV. Interplay between Rac and Rho in the control of substrate contact dynamics. Curr Biol 9: 640‐648, 1999.
 226. Rubinstein B, Fournier MF, Jacobson K, Verkhovsky AB, Mogilner A. Actin‐myosin viscoelastic flow in the keratocyte lamellipod. Biophys J 97: 1853‐1863, 2009.
 227. Rubinstein B, Jacobson K, Mogilner A. Multiscale two‐dimensional modeling of a motile simple‐shaped cell. Multiscale Model Simul 3: 413‐439, 2005.
 228. Sahai E. Mechanisms of cancer cell invasion. Curr Opin Genet Dev 15: 87‐96, 2005.
 229. Sahai E. Illuminating the metastatic process. Nat Rev Cancer 7: 737‐749, 2007.
 230. Sainson RC, Johnston DA, Chu HC, Holderfield MT, Nakatsu MN, Crampton SP, Davis J, Conn E, Hughes CC. TNF primes endothelial cells for angiogenic sprouting by inducing a tip cell phenotype. Blood 111: 4997‐5007, 2008.
 231. Sakakibara A, Furuse M, Saitou M, Ando‐Akatsuka Y, Tsukita S. Possible involvement of phosphorylation of occludin in tight junction formation. J Cell Biol 137: 1393‐1401, 1997.
 232. Sanz‐Moreno V, Marshall CJ. Rho‐GTPase signaling drives melanoma cell plasticity. Cell Cycle 8: 1484‐1487, 2009.
 233. Savill NJ, Hogeweg P. Modelling morphogenesis: From single cells to crawling slugs. J Theor Biol 184: 229‐235, 1997.
 234. Schaller MD. Paxillin: A focal adhesion‐associated adaptor protein. Oncogene 20: 6459‐6472, 2001.
 235. Schaub S, Bohnet S, Laurent VM, Meister JJ, Verkhovsky AB. Comparative maps of motion and assembly of filamentous actin and myosin II in migrating cells. Mol Biol Cell 18: 3723‐3732, 2007.
 236. Schreier T, Degen E, Baschong W. Fibroblast migration and proliferation during in vitro wound healing. A quantitative comparison between various growth factors and a low molecular weight blood dialysate used in the clinic to normalize impaired wound healing. Res Exp Med (Berl) 193: 195‐205, 1993.
 237. Shaw TJ, Martin P. Wound repair at a glance. J Cell Sci 122: 3209‐3213, 2009.
 238. Sherratt JA, Martin P, Murray JD, Lewis J. Mathematical models of wound healing in embryonic and adult epidermis. IMA J Math Appl Med Biol 9: 177‐196, 1992.
 239. Shroff H, Galbraith CG, Galbraith JA, White H, Gillette J, Olenych S, Davidson MW, Betzig E. Dual‐color superresolution imaging of genetically expressed probes within individual adhesion complexes. Proc Natl Acad Sci U S A 104: 20308‐20313, 2007.
 240. Shroff H, White H, Betzig E. Photoactivated localization microscopy (PALM) of adhesion complexes. Curr Protoc Cell Biol 4: 4.21, 2008.
 241. Shtengel G, Galbraith JA, Galbraith CG, Lippincott‐Schwartz J, Gillette JM, Manley S, Sougrat R, Waterman CM, Kanchanawong P, Davidson MW, Fetter RD, Hess HF. Interferometric fluorescent super‐resolution microscopy resolves 3D cellular ultrastructure. Proc Natl Acad Sci U S A 106: 3125‐3130, 2009.
 242. Simpson KJ, Selfors LM, Bui J, Reynolds A, Leake D, Khvorova A, Brugge JS. Identification of genes that regulate epithelial cell migration using an siRNA screening approach. Nat Cell Biol 10: 1027‐1038, 2008.
 243. Simske JS, Hardin J. Getting into shape: Epidermal morphogenesis in Caenorhabditis elegans embryos. Bioessays 23: 12‐23, 2001.
 244. Small JV, Herzog M, Anderson K. Actin filament organization in the fish keratocyte lamellipodium. J Cell Biol 129: 1275‐1286, 1995.
 245. Small JV, Kaverina I. Microtubules meet substrate adhesions to arrange cell polarity. Curr Opin Cell Biol 15: 40‐47, 2003.
 246. Smalley KS, Brafford P, Haass NK, Brandner JM, Brown E, Herlyn M. Up‐regulated expression of zonula occludens protein‐1 in human melanoma associates with N‐cadherin and contributes to invasion and adhesion. Am J Pathol 166: 1541‐1554, 2005.
 247. Solon J, Kaya‐Copur A, Colombelli J, Brunner D. Pulsed forces timed by a ratchet‐like mechanism drive directed tissue movement during dorsal closure. Cell 137: 1331‐1342, 2009.
 248. Suetsugu S, Yamazaki D, Kurisu S, Takenawa T. Differential roles of WAVE1 and WAVE2 in dorsal and peripheral ruffle formation for fibroblast cell migration. Dev Cell 5: 595‐609, 2003.
 249. Svitkina TM, Verkhovsky AB, McQuade KM, Borisy GG. Analysis of the actin‐myosin II system in fish epidermal keratocytes: Mechanism of cell body translocation. J Cell Biol 139: 397‐415, 1997.
 250. Takahisa M, Togashi S, Suzuki T, Kobayashi M, Murayama A, Kondo K, Miyake T, Ueda R. The Drosophila tamou gene, a component of the activating pathway of extramacrochaetae expression, encodes a protein homologous to mammalian cell‐cell junction‐associated protein ZO‐1. Genes Dev 10: 1783‐1795, 1996.
 251. Tambe DT, Corey Hardin C, Angelini TE, Rajendran K, Park CY, Serra‐Picamal X, Zhou EH, Zaman MH, Butler JP, Weitz DA, Fredberg JJ, Trepat X. Collective cell guidance by cooperative intercellular forces. Nat Mater 10: 469‐475, 2011.
 252. Tan JL, Tien J, Pirone DM, Gray DS, Bhadriraju K, Chen CS. Cells lying on a bed of microneedles: An approach to isolate mechanical force. Proc Natl Acad Sci U S A 100: 1484‐1489, 2003.
 253. Tavella S, Bellese G, Castagnola P, Martin I, Piccini D, Doliana R, Colombatti A, Cancedda R, Tacchetti C. Regulated expression of fibronectin, laminin and related integrin receptors during the early chondrocyte differentiation. J Cell Sci 110(Pt 18): 2261‐2270, 1997.
 254. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial‐mesenchymal transitions in development and disease. Cell 139: 871‐890, 2009.
 255. Thoreson MA, Anastasiadis PZ, Daniel JM, Ireton RC, Wheelock MJ, Johnson KR, Hummingbird DK, Reynolds AB. Selective uncoupling of p120(ctn) from E‐cadherin disrupts strong adhesion. J Cell Biol 148: 189‐202, 2000.
 256. Tonnesen MG, Feng X, Clark RA. Angiogenesis in wound healing. J Invest Derm Symp Proc 5: 40‐46, 2000.
 257. Toriseva M, Kahari VM. Proteinases in cutaneous wound healing. Cell Mol Life Sci 66: 203‐224, 2009.
 258. Toyama Y, Peralta XG, Wells AR, Kiehart DP, Edwards GS. Apoptotic force and tissue dynamics during Drosophila embryogenesis. Science 321: 1683‐1686, 2008.
 259. Trepat X, Grabulosa M, Buscemi L, Rico F, Farre R, Navajas D. Thrombin and histamine induce stiffening of alveolar epithelial cells. J Appl Physiol 98: 1567‐1574, 2005.
 260. Trepat X, Wasserman MR, Angelini TE, Millet E, Weitz DA, Butler JP, Fredberg JJ. Physical forces during collective cell migration. Nature Phys 5: 426, 2009.
 261. Turner CE. Paxillin interactions. J Cell Sci 113(Pt 23): 4139‐4140, 2000.
 262. Urban E, Jacob S, Nemethova M, Resch GP, Small JV. Electron tomography reveals unbranched networks of actin filaments in lamellipodia. Nat Cell Biol 12: 429‐435, 2010.
 263. Uv A, Cantera R, Samakovlis C. Drosophila tracheal morphogenesis: Intricate cellular solutions to basic plumbing problems. Trends Cell Biol 13: 301‐309, 2003.
 264. Valentin G, Haas P, Gilmour D. The chemokine SDF1a coordinates tissue migration through the spatially restricted activation of Cxcr7 and Cxcr4b. Curr Biol 17: 1026‐1031, 2007.
 265. Vallotton P, Danuser G, Bohnet S, Meister JJ, Verkhovsky AB. Tracking retrograde flow in keratocytes: News from the front. Mol Biol Cell 16: 1223‐1231, 2005.
 266. van Roy F, Berx G. The cell‐cell adhesion molecule E‐cadherin. Cell Mol Life Sci 65: 3756‐3788, 2008.
 267. Verkhovsky AB, Chaga OY, Schaub S, Svitkina TM, Meister JJ, Borisy GG. Orientational order of the lamellipodial actin network as demonstrated in living motile cells. Mol Biol Cell 14: 4667‐4675, 2003.
 268. Verkhovsky AB, Svitkina TM, Borisy GG. Self‐polarization and directional motility of cytoplasm. Curr Biol 9: 11‐20, 1999.
 269. Vestweber D, Kemler R. Identification of a putative cell adhesion domain of uvomorulin. EMBO J 4: 3393‐3398, 1985.
 270. Vicente‐Manzanares M, Zareno J, Whitmore L, Choi CK, Horwitz AF. Regulation of protrusion, adhesion dynamics, and polarity by myosins IIA and IIB in migrating cells. J Cell Biol 176: 573‐580, 2007.
 271. Virchow R. Uber bewegliche thierische zellen. Arch Path Anat 28: 237‐240, 1863.
 272. Vitorino P, Meyer T. Modular control of endothelial sheet migration. Genes Dev 22: 3268‐3281, 2008.
 273. Wallis S, Lloyd S, Wise I, Ireland G, Fleming TP, Garrod D. The alpha isoform of protein kinase C is involved in signaling the response of desmosomes to wounding in cultured epithelial cells. Mol Biol Cell 11: 1077‐1092, 2000.
 274. Wang Y‐L, Dembo M, Wang H‐B, Lo C‐M. Cell movement is guided by the rigidity of the substrate. Biophys J 79: 144‐152, 2000.
 275. Wang YL, Pelhan RJ. Preparation of a flexible, porous polyacrylamide substrate for mechanical studies of cultured cells. Methods Enzymol 298: 489‐496, 1998.
 276. Ware MF, Wells A, Lauffenburger DA. Epidermal growth factor alters fibroblast migration speed and directional persistence reciprocally and in a matrix‐dependent manner. J Cell Sci 111(Pt 16): 2423‐2432, 1998.
 277. Watanabe T, Costantini F. Real‐time analysis of ureteric bud branching morphogenesis in vitro. Dev Biol 271: 98‐108, 2004.
 278. Webb DJ, Donais K, Whitmore LA, Thomas SM, Turner CE, Parsons JT, Horwitz AF. FAK‐Src signalling through paxillin, ERK and MLCK regulates adhesion disassembly. Nat Cell Biol 6: 154‐161, 2004.
 279. Webb DJ, Parsons JT, Horwitz AF. Adhesion assembly, disassembly and turnover in migrating cells – over and over and over again. Nat Cell Biol 4: E97‐E100, 2002.
 280. Wegener KL, Partridge AW, Han J, Pickford AR, Liddington RC, Ginsberg MH, Campbell ID. Structural basis of integrin activation by talin. Cell 128: 171‐182, 2007.
 281. Weijer CJ. Collective cell migration in development. J Cell Sci 122: 3215‐3223, 2009.
 282. Werner S, Grose R. Regulation of wound healing by growth factors and cytokines. Physiol Rev 83: 835‐870, 2003.
 283. Wilson CA, Tsuchida MA, Allen GM, Barnhart EL, Applegate KT, Yam PT, Ji L, Keren K, Danuser G, Theriot JA. Myosin II contributes to cell‐scale actin network treadmilling through network disassembly. Nature 465: 373‐377, 2010.
 284. Wolf K, Alexander S, Schacht V, Coussens LM, von Andrian UH, van Rheenen J, Deryugina E, Friedl P. Collagen‐based cell migration models in vitro and in vivo. Semin Cell Dev Biol 20: 931‐941, 2009.
 285. Wolf K, Mazo I, Leung H, Engelke K, von Andrian UH, Deryugina EI, Strongin AY, Brocker EB, Friedl P. Compensation mechanism in tumor cell migration: Mesenchymal‐amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160: 267‐277, 2003.
 286. Wolf K, Wu YI, Liu Y, Geiger J, Tam E, Overall C, Stack MS, Friedl P. Multi‐step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9: 893‐904, 2007.
 287. Wood W, Jacinto A, Grose R, Woolner S, Gale J, Wilson C, Martin P. Wound healing recapitulates morphogenesis in Drosophila embryos. Nat Cell Biol 4: 907‐912, 2002.
 288. Worthylake RA, Burridge K. Leukocyte transendothelial migration: Orchestrating the underlying molecular machinery. Curr Opin Cell Biol 13: 569‐577, 2001.
 289. Xu X, Francis R, Wei CJ, Linask KL, Lo CW. Connexin 43‐mediated modulation of polarized cell movement and the directional migration of cardiac neural crest cells. Development 133: 3629‐3639, 2006.
 290. Yamada S, Pokutta S, Drees F, Weis WI, Nelson WJ. Deconstructing the cadherin‐catenin‐actin complex. Cell 123: 889‐901, 2005.
 291. Yamamoto E, Kohama G, Sunakawa H, Iwai M, Hiratsuka H. Mode of invasion, bleomycin sensitivity, and clinical course in squamous cell carcinoma of the oral cavity. Cancer 51: 2175‐2180, 1983.
 292. Yap AS, Crampton MS, Hardin J. Making and breaking contacts: The cellular biology of cadherin regulation. Curr Opin Cell Biol 19: 508‐514, 2007.
 293. Yap AS, Niessen CM, Gumbiner BM. The juxtamembrane region of the cadherin cytoplasmic tail supports lateral clustering, adhesive strengthening, and interaction with p120ctn. J Cell Biol 141: 779‐789, 1998.
 294. Zaidel‐Bar R, Cohen M, Addadi L, Geiger B. Hierarchical assembly of cell‐matrix adhesion complexes. Biochem Soc Trans 32: 416‐420, 2004.
 295. Zamir E, Geiger B. Molecular complexity and dynamics of cell‐matrix adhesions. J Cell Sci 114: 3583‐3590, 2001.

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Article Title: Cell Migration
 

How to Cite

Xavier Trepat, Zaozao Chen, Ken Jacobson. Cell Migration. Compr Physiol 2012, 2: 2369-2392. doi: 10.1002/cphy.c110012