Skip to main content

Advertisement

SpringerLink
Log in

Small Rho GTPases in the control of cell shape and mobility

  • Review
  • Published:
Cellular and Molecular Life Sciences Aims and scope Submit manuscript

Abstract

Rho GTPases are a class of evolutionarily conserved proteins comprising 20 members, which are predominantly known for their role in regulating the actin cytoskeleton. They are primarily regulated by binding of GTP/GDP, which is again controlled by regulators like GEFs, GAPs, and RhoGDIs. Rho GTPases are thus far well known for their role in the regulation of actin cytoskeleton and migration. Here we present an overview on the role of Rho GTPases in regulating cell shape and plasticity of cell migration. Finally, we discuss the emerging roles of ubiquitination and sumoylation in regulating Rho GTPases and cell migration.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5
Fig. 6
Fig. 7

Similar content being viewed by others

References

  1. Valencia A, Chardin P, Wittinghofer A, Sander C (1991) The Ras protein family: evolutionary tree and role of conserved amino acids. Biochemistry 30:4637–4648

    PubMed  CAS  Google Scholar 

  2. Sahai E, Marshall CJ (2002) RHO-GTPases and cancer. Nat Rev Cancer 2:133–142

    PubMed  Google Scholar 

  3. Jaiswal M, Fansa EK, Dvorsky R, Ahmadian MR (2013) New insight into the molecular switch mechanism of human Rho family proteins: shifting a paradigm. Biol Chem 394:89–95

    PubMed  CAS  Google Scholar 

  4. Aspenstrom P, Ruusala A, Pacholsky D (2007) Taking Rho GTPases to the next level: the cellular functions of atypical Rho GTPases. Exp Cell Res 313:3673–3679

    PubMed  Google Scholar 

  5. Chardin P (2006) Function and regulation of Rnd proteins. Nat Rev Mol Cell Biol 7:54–62

    PubMed  CAS  Google Scholar 

  6. Wherlock M, Mellor H (2002) The Rho GTPase family: a Racs to Wrchs story. J Cell Sci 115:239–240

    PubMed  CAS  Google Scholar 

  7. Ongusaha PP, Kim HG, Boswell SA, Ridley AJ, Der CJ, Dotto GP, Kim YB, Aaronson SA, Lee SW (2006) RhoE is a pro-survival p53 target gene that inhibits ROCK I-mediated apoptosis in response to genotoxic stress. Curr Biol 16:2466–2472

    PubMed Central  PubMed  CAS  Google Scholar 

  8. Tao W, Pennica D, Xu L, Kalejta RF, Levine AJ (2001) Wrch-1, a novel member of the Rho gene family that is regulated by Wnt-1. Genes Dev 15:1796–1807

    PubMed Central  PubMed  CAS  Google Scholar 

  9. Jaffe AB, Hall A (2005) Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol 21:247–269

    PubMed  CAS  Google Scholar 

  10. Boureux A, Vignal E, Faure S, Fort P (2007) Evolution of the Rho family of Ras-like GTPases in eukaryotes. Mol Biol Evol 24:203–216

    PubMed Central  PubMed  CAS  Google Scholar 

  11. Eden S, Rohatgi R, Podtelejnikov AV, Mann M, Kirschner MW (2002) Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. Nature 418:790–793

    PubMed  CAS  Google Scholar 

  12. Machacek M, Hodgson L, Welch C, Elliott H, Pertz O, Nalbant P, Abell A, Johnson GL, Hahn KM, Danuser G (2009) Coordination of Rho GTPase activities during cell protrusion. Nature 461:99–103

    PubMed Central  PubMed  CAS  Google Scholar 

  13. Thiel DA, Reeder MK, Pfaff A, Coleman TR, Sells MA, Chernoff J (2002) Cell cycle-regulated phosphorylation of p21-activated kinase 1. Curr Biol 12:1227–1232

    PubMed  CAS  Google Scholar 

  14. Wells CM, Walmsley M, Ooi S, Tybulewicz V, Ridley AJ (2004) Rac1-deficient macrophages exhibit defects in cell spreading and membrane ruffling but not migration. J Cell Sci 117:1259–1268

    PubMed  CAS  Google Scholar 

  15. Wu YI, Wang X, He L, Montell D, Hahn KM (2011) Spatiotemporal control of small GTPases with light using the LOV domain. Methods Enzymol 497:393–407

    PubMed Central  PubMed  CAS  Google Scholar 

  16. Wu YI, Frey D, Lungu OI, Jaehrig A, Schlichting I, Kuhlman B, Hahn KM (2009) A genetically encoded photoactivatable Rac controls the motility of living cells. Nature 461:104–108

    PubMed Central  PubMed  CAS  Google Scholar 

  17. Wang X, He L, Wu YI, Hahn KM, Montell DJ (2010) Light-mediated activation reveals a key role for Rac in collective guidance of cell movement in vivo. Nat Cell Biol 12:591–597

    PubMed Central  PubMed  CAS  Google Scholar 

  18. Zhang Y, Rivera Rosado LA, Moon SY, Zhang B (2009) Silencing of D4-GDI inhibits growth and invasive behavior in MDA-MB-231 cells by activation of Rac-dependent p38 and JNK signaling. J Biol Chem 284:12956–12965

    PubMed Central  PubMed  CAS  Google Scholar 

  19. Chen L, Zhang JJ, Huang XY (2008) cAMP inhibits cell migration by interfering with Rac-induced lamellipodium formation. J Biol Chem 283:13799–13805

    PubMed Central  PubMed  CAS  Google Scholar 

  20. Sala G, Dituri F, Raimondi C, Previdi S, Maffucci T, Mazzoletti M, Rossi C, Iezzi M, Lattanzio R, Piantelli M, Iacobelli S, Broggini M, Falasca M (2008) Phospholipase Cgamma1 is required for metastasis development and progression. Cancer Res 68:10187–10196

    PubMed  CAS  Google Scholar 

  21. Mullins RD, Heuser JA, Pollard TD (1998) The interaction of Arp2/3 complex with actin: nucleation, high affinity pointed end capping, and formation of branching networks of filaments. Proc Natl Acad Sci USA 95:6181–6186

    PubMed Central  PubMed  CAS  Google Scholar 

  22. Bokoch GM (2000) Regulation of cell function by Rho family GTPases. Immunol Res 21:139–148

    PubMed  CAS  Google Scholar 

  23. Edwards DC, Sanders LC, Bokoch GM, Gill GN (1999) Activation of LIM-kinase by Pak1 couples Rac/Cdc42 GTPase signalling to actin cytoskeletal dynamics. Nat Cell Biol 1:253–259

    PubMed  CAS  Google Scholar 

  24. Vadlamudi RK, Li F, Barnes CJ, Bagheri-Yarmand R, Kumar R (2004) p41-Arc subunit of human Arp2/3 complex is a p21-activated kinase-1-interacting substrate. EMBO Rep 5:154–160

    PubMed Central  PubMed  CAS  Google Scholar 

  25. Ong CC, Jubb AM, Zhou W, Haverty PM, Harris AL, Belvin M, Friedman LS, Koeppen H, Hoeflich KP (2011) p21-activated kinase 1: PAK’ed with potential. Oncotarget 2:491–496

    PubMed Central  PubMed  Google Scholar 

  26. Rayala SK, Molli PR, Kumar R (2006) Nuclear p21-activated kinase 1 in breast cancer packs off tamoxifen sensitivity. Cancer Res 66:5985–5988

    PubMed  CAS  Google Scholar 

  27. Sugihara K, Nakatsuji N, Nakamura K, Nakao K, Hashimoto R, Otani H, Sakagami H, Kondo H, Nozawa S, Aiba A, Katsuki M (1998) Rac1 is required for the formation of three germ layers during gastrulation. Oncogene 17:3427–3433

    PubMed  CAS  Google Scholar 

  28. Benninger Y, Thurnherr T, Pereira JA, Krause S, Wu X, Chrostek-Grashoff A, Herzog D, Nave KA, Franklin RJ, Meijer D, Brakebusch C, Suter U, Relvas JB (2007) Essential and distinct roles for cdc42 and rac1 in the regulation of Schwann cell biology during peripheral nervous system development. J Cell Biol 177:1051–1061

    PubMed Central  PubMed  CAS  Google Scholar 

  29. Guo F, Cancelas JA, Hildeman D, Williams DA, Zheng Y (2008) Rac GTPase isoforms Rac1 and Rac2 play a redundant and crucial role in T-cell development. Blood 112:1767–1775

    PubMed Central  PubMed  CAS  Google Scholar 

  30. Walmsley MJ, Ooi SK, Reynolds LF, Smith SH, Ruf S, Mathiot A, Vanes L, Williams DA, Cancro MP, Tybulewicz VL (2003) Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling. Science 302:459–462

    PubMed  CAS  Google Scholar 

  31. Heasman SJ, Ridley AJ (2008) Mammalian Rho GTPases: new insights into their functions from in vivo studies. Nat Rev Mol Cell Biol 9:690–701

    PubMed  CAS  Google Scholar 

  32. Corbetta S, Gualdoni S, Albertinazzi C, Paris S, Croci L, Consalez GG, de Curtis I (2005) Generation and characterization of Rac3 knockout mice. Mol Cell Biol 25:5763–5776

    PubMed Central  PubMed  CAS  Google Scholar 

  33. Hodis E, Watson IR, Kryukov GV, Arold ST, Imielinski M, Theurillat JP, Nickerson E, Auclair D, Li L, Place C, Dicara D, Ramos AH, Lawrence MS, Cibulskis K, Sivachenko A, Voet D, Saksena G, Stransky N, Onofrio RC, Winckler W, Ardlie K, Wagle N, Wargo J, Chong K, Morton DL, Stemke-Hale K, Chen G, Noble M, Meyerson M, Ladbury JE, Davies MA, Gershenwald JE, Wagner SN, Hoon DS, Schadendorf D, Lander ES, Gabriel SB, Getz G, Garraway LA, Chin L (2012) A landscape of driver mutations in melanoma. Cell 150:251–263

    PubMed Central  PubMed  CAS  Google Scholar 

  34. Krauthammer M, Kong Y, Ha BH, Evans P, Bacchiocchi A, McCusker JP, Cheng E, Davis MJ, Goh G, Choi M, Ariyan S, Narayan D, Dutton-Regester K, Capatana A, Holman EC, Bosenberg M, Sznol M, Kluger HM, Brash DE, Stern DF, Materin MA, Lo RS, Mane S, Ma S, Kidd KK, Hayward NK, Lifton RP, Schlessinger J, Boggon TJ, Halaban R (2012) Exome sequencing identifies recurrent somatic RAC1 mutations in melanoma. Nat Genet 44:1006–1014

    PubMed Central  PubMed  CAS  Google Scholar 

  35. Jordan P, Brazao R, Boavida MG, Gespach C, Chastre E (1999) Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors. Oncogene 18:6835–6839

    PubMed  CAS  Google Scholar 

  36. Matos P, Collard JG, Jordan P (2003) Tumor-related alternatively spliced Rac1b is not regulated by Rho-GDP dissociation inhibitors and exhibits selective downstream signaling. J Biol Chem 278:50442–50448

    PubMed  CAS  Google Scholar 

  37. Singh A, Karnoub AE, Palmby TR, Lengyel E, Sondek J, Der CJ (2004) Rac1b, a tumor associated, constitutively active Rac1 splice variant, promotes cellular transformation. Oncogene 23:9369–9380

    PubMed  CAS  Google Scholar 

  38. Visvikis O, Lores P, Boyer L, Chardin P, Lemichez E, Gacon G (2008) Activated Rac1, but not the tumorigenic variant Rac1b, is ubiquitinated on Lys 147 through a JNK-regulated process. FEBS J 275:386–396

    PubMed  CAS  Google Scholar 

  39. Ladd PD, Butler JS, Skalnik DG (2004) Identification of a genomic fragment that directs hematopoietic-specific expression of Rac2 and analysis of the DNA methylation profile of the gene locus. Gene 341:323–333

    PubMed  CAS  Google Scholar 

  40. Haataja L, Groffen J, Heisterkamp N (1997) Characterization of RAC3, a novel member of the Rho family. J Biol Chem 272:20384–20388

    PubMed  CAS  Google Scholar 

  41. Van Hennik PB, Hordijk PL (2005) Rho GTPases in hematopoietic cells. Antioxid Redox Signal 7:1440–1455

    PubMed  Google Scholar 

  42. Roberts AW, Kim C, Zhen L, Lowe JB, Kapur R, Petryniak B, Spaetti A, Pollock JD, Borneo JB, Bradford GB, Atkinson SJ, Dinauer MC, Williams DA (1999) Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. Immunity 10:183–196

    PubMed  CAS  Google Scholar 

  43. Williams DA, Tao W, Yang F, Kim C, Gu Y, Mansfield P, Levine JE, Petryniak B, Derrow CW, Harris C, Jia B, Zheng Y, Ambruso DR, Lowe JB, Atkinson SJ, Dinauer MC, Boxer L (2000) Dominant negative mutation of the hematopoietic-specific Rho GTPase, Rac2, is associated with a human phagocyte immunodeficiency. Blood 96:1646–1654

    PubMed  CAS  Google Scholar 

  44. Yamauchi A, Kim C, Li S, Marchal CC, Towe J, Atkinson SJ, Dinauer MC (2004) Rac2-deficient murine macrophages have selective defects in superoxide production and phagocytosis of opsonized particles. J Immunol 173:5971–5979

    PubMed  CAS  Google Scholar 

  45. Dinauer MC (2003) Regulation of neutrophil function by Rac GTPases. Curr Opin Hematol 10:8–15

    PubMed  CAS  Google Scholar 

  46. Werner E (2004) GTPases and reactive oxygen species: switches for killing and signaling. J Cell Sci 117:143–153

    PubMed  CAS  Google Scholar 

  47. Mira JP, Benard V, Groffen J, Sanders LC, Knaus UG (2000) Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway. Proc Natl Acad Sci USA 97:185–189

    PubMed Central  PubMed  CAS  Google Scholar 

  48. Morris CM, Haataja L, McDonald M, Gough S, Markie D, Groffen J, Heisterkamp N (2000) The small GTPase RAC3 gene is located within chromosome band 17q25.3 outside and telomeric of a region commonly deleted in breast and ovarian tumours. Cytogenet Cell Genet 89:18–23

    PubMed  CAS  Google Scholar 

  49. Katoh H, Hiramoto K, Negishi M (2006) Activation of Rac1 by RhoG regulates cell migration. J Cell Sci 119:56–65

    PubMed  CAS  Google Scholar 

  50. Patel JC, Galan JE (2008) Investigating the function of Rho family GTPases during Salmonella/host cell interactions. Methods Enzymol 439:145–158

    PubMed Central  PubMed  CAS  Google Scholar 

  51. Roppenser B, Roder A, Hentschke M, Ruckdeschel K, Aepfelbacher M (2009) Yersinia enterocolitica differentially modulates RhoG activity in host cells. J Cell Sci 122:696–705

    PubMed  CAS  Google Scholar 

  52. Samson T, Welch C, Monaghan-Benson E, Hahn KM, Burridge K (2010) Endogenous RhoG is rapidly activated after epidermal growth factor stimulation through multiple guanine-nucleotide exchange factors. Mol Biol Cell 21:1629–1642

    PubMed Central  PubMed  CAS  Google Scholar 

  53. Yang HW, Shin MG, Lee S, Kim JR, Park WS, Cho KH, Meyer T, Do Heo W (2012) Cooperative activation of PI3K by Ras and Rho family small GTPases. Mol Cell 47:281–290

    PubMed Central  PubMed  CAS  Google Scholar 

  54. Gomez del Pulgar T, Benitah SA, Valeron PF, Espina C, Lacal JC (2005) Rho GTPase expression in tumourigenesis: evidence for a significant link. BioEssays 27:602–613

    PubMed  Google Scholar 

  55. Huang M, Prendergast GC (2006) RhoB in cancer suppression. Histol Histopathol 21:213–218

    PubMed  CAS  Google Scholar 

  56. Ridley AJ (2013) RhoA, RhoB and RhoC have different roles in cancer cell migration. J Microsc 251:242–249

    PubMed  CAS  Google Scholar 

  57. Braga VM, Yap AS (2005) The challenges of abundance: epithelial junctions and small GTPase signalling. Curr Opin Cell Biol 17:466–474

    PubMed  CAS  Google Scholar 

  58. Friedl P, Wolf K (2003) Tumour-cell invasion and migration: diversity and escape mechanisms. Nat Rev Cancer 3:362–374

    PubMed  CAS  Google Scholar 

  59. Merajver SD, Usmani SZ (2005) Multifaceted role of Rho proteins in angiogenesis. J Mammary Gland Biol Neoplasia 10:291–298

    PubMed  Google Scholar 

  60. Wang W, Wu F, Fang F, Tao Y, Yang L (2008) RhoC is essential for angiogenesis induced by hepatocellular carcinoma cells via regulation of endothelial cell organization. Cancer Sci 99:2012–2018

    PubMed  CAS  Google Scholar 

  61. Dietrich KA, Schwarz R, Liska M, Grass S, Menke A, Meister M, Kierschke G, Langle C, Genze F, Giehl K (2009) Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activity. Biol Chem 390:1063–1077

    PubMed  CAS  Google Scholar 

  62. Ellis S, Mellor H (2000) Regulation of endocytic traffic by rho family GTPases. Trends Cell Biol 10:85–88

    PubMed  CAS  Google Scholar 

  63. Ridley AJ (2006) Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. Trends Cell Biol 16:522–529

    PubMed  CAS  Google Scholar 

  64. Liu AX, Rane N, Liu JP, Prendergast GC (2001) RhoB is dispensable for mouse development, but it modifies susceptibility to tumor formation as well as cell adhesion and growth factor signaling in transformed cells. Mol Cell Biol 21:6906–6912

    PubMed Central  PubMed  CAS  Google Scholar 

  65. Ho TT, Merajver SD, Lapiere CM, Nusgens BV, Deroanne CF (2008) RhoA-GDP regulates RhoB protein stability. Potential involvement of RhoGDIalpha. J Biol Chem 283:21588–21598

    PubMed  CAS  Google Scholar 

  66. Vega FM, Fruhwirth G, Ng T, Ridley AJ (2011) RhoA and RhoC have distinct roles in migration and invasion by acting through different targets. J Cell Biol 193:655–665

    PubMed Central  PubMed  CAS  Google Scholar 

  67. Lang P, Gesbert F, Delespine-Carmagnat M, Stancou R, Pouchelet M, Bertoglio J (1996) Protein kinase A phosphorylation of RhoA mediates the morphological and functional effects of cyclic AMP in cytotoxic lymphocytes. EMBO J 15:510–519

    PubMed Central  PubMed  CAS  Google Scholar 

  68. Sauzeau V, Le Jeune H, Cario-Toumaniantz C, Smolenski A, Lohmann SM, Bertoglio J, Chardin P, Pacaud P, Loirand G (2000) Cyclic GMP-dependent protein kinase signaling pathway inhibits RhoA-induced Ca2+ sensitization of contraction in vascular smooth muscle. J Biol Chem 275:21722–21729

    PubMed  CAS  Google Scholar 

  69. Savoia C, Tabet F, Yao G, Schiffrin EL, Touyz RM (2005) Negative regulation of RhoA/Rho kinase by angiotensin II type 2 receptor in vascular smooth muscle cells: role in angiotensin II-induced vasodilation in stroke-prone spontaneously hypertensive rats. J Hypertens 23:1037–1045

    PubMed  CAS  Google Scholar 

  70. Sloan CM, Quinn CV, Peters JP, Farley J, Goetzinger C, Wernli M, DeMali KA, Ellerbroek SM (2012) Divergence of Rho residue 43 impacts GEF activity. Small GTPases 3:15–22

    PubMed Central  PubMed  Google Scholar 

  71. Garvalov BK, Flynn KC, Neukirchen D, Meyn L, Teusch N, Wu X, Brakebusch C, Bamburg JR, Bradke F (2007) Cdc42 regulates cofilin during the establishment of neuronal polarity. J Neurosci 27:13117–13129

    PubMed  CAS  Google Scholar 

  72. Thurnherr T, Benninger Y, Wu X, Chrostek A, Krause SM, Nave KA, Franklin RJ, Brakebusch C, Suter U, Relvas JB (2006) Cdc42 and Rac1 signaling are both required for and act synergistically in the correct formation of myelin sheaths in the CNS. J Neurosci 26:10110–10119

    PubMed  CAS  Google Scholar 

  73. Lee K, Boyd KL, Parekh DV, Kehl-Fie TE, Baldwin HS, Brakebusch C, Skaar EP, Boothby M, Zent R (2013) Cdc42 promotes host defenses against fatal infection. Infect Immun 81:2714–2723

    PubMed Central  PubMed  CAS  Google Scholar 

  74. Yang L, Wang L, Zheng Y (2006) Gene targeting of Cdc42 and Cdc42GAP affirms the critical involvement of Cdc42 in filopodia induction, directed migration, and proliferation in primary mouse embryonic fibroblasts. Mol Biol Cell 17:4675–4685

    PubMed Central  PubMed  CAS  Google Scholar 

  75. Czuchra A, Wu X, Meyer H, van Hengel J, Schroeder T, Geffers R, Rottner K, Brakebusch C (2005) Cdc42 is not essential for filopodium formation, directed migration, cell polarization, and mitosis in fibroblastoid cells. Mol Biol Cell 16:4473–4484

    PubMed Central  PubMed  CAS  Google Scholar 

  76. Chiang SH, Baumann CA, Kanzaki M, Thurmond DC, Watson RT, Neudauer CL, Macara IG, Pessin JE, Saltiel AR (2001) Insulin-stimulated GLUT4 translocation requires the CAP-dependent activation of TC10. Nature 410:944–948

    PubMed  CAS  Google Scholar 

  77. Kawase K, Nakamura T, Takaya A, Aoki K, Namikawa K, Kiyama H, Inagaki S, Takemoto H, Saltiel AR, Matsuda M (2006) GTP hydrolysis by the Rho family GTPase TC10 promotes exocytic vesicle fusion. Dev Cell 11:411–421

    PubMed  CAS  Google Scholar 

  78. Abe T, Kato M, Miki H, Takenawa T, Endo T (2003) Small GTPase Tc10 and its homologue RhoT induce N-WASP-mediated long process formation and neurite outgrowth. J Cell Sci 116:155–168

    PubMed  CAS  Google Scholar 

  79. Doyle AD, Petrie RJ, Kutys ML, Yamada KM (2013) Dimensions in cell migration. Curr Opin Cell Biol 25:642–649

    PubMed  CAS  Google Scholar 

  80. Petrie RJ, Yamada KM (2012) At the leading edge of three-dimensional cell migration. J Cell Sci 125:5917–5926

    PubMed  CAS  Google Scholar 

  81. Charras GT, Yarrow JC, Horton MA, Mahadevan L, Mitchison TJ (2005) Non-equilibration of hydrostatic pressure in blebbing cells. Nature 435:365–369

    PubMed Central  PubMed  CAS  Google Scholar 

  82. Linder S, Wiesner C, Himmel M (2011) Degrading devices: invadosomes in proteolytic cell invasion. Annu Rev Cell Dev Biol 27:185–211

    PubMed  CAS  Google Scholar 

  83. Provenzano PP, Inman DR, Eliceiri KW, Trier SM, Keely PJ (2008) Contact guidance mediated three-dimensional cell migration is regulated by Rho/ROCK-dependent matrix reorganization. Biophys J 95:5374–5384

    PubMed Central  PubMed  CAS  Google Scholar 

  84. Sidani M, Wyckoff J, Xue C, Segall JE, Condeelis J (2006) Probing the microenvironment of mammary tumors using multiphoton microscopy. J Mammary Gland Biol Neoplasia 11:151–163

    PubMed  Google Scholar 

  85. Baker BM, Chen CS (2012) Deconstructing the third dimension: how 3D culture microenvironments alter cellular cues. J Cell Sci 125:3015–3024

    PubMed Central  PubMed  CAS  Google Scholar 

  86. Giampieri S, Manning C, Hooper S, Jones L, Hill CS, Sahai E (2009) Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility. Nat Cell Biol 11:1287–1296

    PubMed Central  PubMed  CAS  Google Scholar 

  87. Grinnell F (2008) Fibroblast mechanics in three-dimensional collagen matrices. J Bodyw Mov Ther 12:191–193

    PubMed Central  PubMed  Google Scholar 

  88. Sanz-Moreno V, Gadea G, Ahn J, Paterson H, Marra P, Pinner S, Sahai E, Marshall CJ (2008) Rac activation and inactivation control plasticity of tumor cell movement. Cell 135:510–523

    PubMed  CAS  Google Scholar 

  89. Lee HH, Tien SC, Jou TS, Chang YC, Jhong JG, Chang ZF (2010) Src-dependent phosphorylation of ROCK participates in regulation of focal adhesion dynamics. J Cell Sci 123:3368–3377

    PubMed  CAS  Google Scholar 

  90. Etienne-Manneville S, Hall A (2001) Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. Cell 106:489–498

    PubMed  CAS  Google Scholar 

  91. Ridley AJ, Schwartz MA, Burridge K, Firtel RA, Ginsberg MH, Borisy G, Parsons JT, Horwitz AR (2003) Cell migration: integrating signals from front to back. Science 302:1704–1709

    PubMed  CAS  Google Scholar 

  92. Yui Y, Itoh K, Yoshioka K, Naka N, Watanabe M, Hiraumi Y, Matsubara H, Watanabe K, Sano K, Nakahata T, Adachi S (2010) Mesenchymal mode of migration participates in pulmonary metastasis of mouse osteosarcoma LM8. Clin Exp Metastasis 27:619–630

    PubMed  CAS  Google Scholar 

  93. Block J, Breitsprecher D, Kuhn S, Winterhoff M, Kage F, Geffers R, Duwe P, Rohn JL, Baum B, Brakebusch C, Geyer M, Stradal TE, Faix J, Rottner K (2012) FMNL2 drives actin-based protrusion and migration downstream of Cdc42. Curr Biol 22:1005–1012

    PubMed Central  PubMed  CAS  Google Scholar 

  94. Alblas J, Ulfman L, Hordijk P, Koenderman L (2001) Activation of Rhoa and ROCK are essential for detachment of migrating leukocytes. Mol Biol Cell 12:2137–2145

    PubMed Central  PubMed  CAS  Google Scholar 

  95. Kurokawa K, Matsuda M (2005) Localized RhoA activation as a requirement for the induction of membrane ruffling. Mol Biol Cell 16:4294–4303

    PubMed Central  PubMed  CAS  Google Scholar 

  96. Bachy S, Letourneur F, Rousselle P (2008) Syndecan-1 interaction with the LG4/5 domain in laminin-332 is essential for keratinocyte migration. J Cell Physiol 214:238–249

    PubMed  CAS  Google Scholar 

  97. Gonzalo P, Guadamillas MC, Hernandez-Riquer MV, Pollan A, Grande-Garcia A, Bartolome RA, Vasanji A, Ambrogio C, Chiarle R, Teixido J, Risteli J, Apte SS, del Pozo MA, Arroyo AG (2010) MT1-MMP is required for myeloid cell fusion via regulation of Rac1 signaling. Dev Cell 18:77–89

    PubMed Central  PubMed  CAS  Google Scholar 

  98. Kheradmand F, Werner E, Tremble P, Symons M, Werb Z (1998) Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change. Science 280:898–902

    PubMed  CAS  Google Scholar 

  99. Westermarck J, Kahari VM (1999) Regulation of matrix metalloproteinase expression in tumor invasion. Faseb J 13:781–792

    PubMed  CAS  Google Scholar 

  100. Yamagata K, Li X, Ikegaki S, Oneyama C, Okada M, Nishita M, Minami Y (2012) Dissection of Wnt5a-Ror2 signaling leading to matrix metalloproteinase (MMP-13) expression. J Biol Chem 287:1588–1599

    PubMed Central  PubMed  CAS  Google Scholar 

  101. Jeong KJ, Park SY, Cho KH, Sohn JS, Lee J, Kim YK, Kang J, Park CG, Han JW, Lee HY (2012) The Rho/ROCK pathway for lysophosphatidic acid-induced proteolytic enzyme expression and ovarian cancer cell invasion. Oncogene 31:4279–4289

    PubMed  CAS  Google Scholar 

  102. Wyckoff JB, Jones JG, Condeelis JS, Segall JE (2000) A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. Cancer Res 60:2504–2511

    PubMed  CAS  Google Scholar 

  103. Philippar U, Roussos ET, Oser M, Yamaguchi H, Kim HD, Giampieri S, Wang Y, Goswami S, Wyckoff JB, Lauffenburger DA, Sahai E, Condeelis JS, Gertler FB (2008) A Mena invasion isoform potentiates EGF-induced carcinoma cell invasion and metastasis. Dev Cell 15:813–828

    PubMed Central  PubMed  CAS  Google Scholar 

  104. Sahai E, Wyckoff J, Philippar U, Segall JE, Gertler F, Condeelis J (2005) Simultaneous imaging of GFP, CFP and collagen in tumors in vivo using multiphoton microscopy. BMC Biotechnol 5:14

    PubMed Central  PubMed  Google Scholar 

  105. Xue C, Wyckoff J, Liang F, Sidani M, Violini S, Tsai KL, Zhang ZY, Sahai E, Condeelis J, Segall JE (2006) Epidermal growth factor receptor overexpression results in increased tumor cell motility in vivo coordinately with enhanced intravasation and metastasis. Cancer Res 66:192–197

    PubMed  CAS  Google Scholar 

  106. Fackler OT, Grosse R (2008) Cell motility through plasma membrane blebbing. J Cell Biol 181:879–884

    PubMed Central  PubMed  CAS  Google Scholar 

  107. Keller HU, Bebie H (1996) Protrusive activity quantitatively determines the rate and direction of cell locomotion. Cell Motil Cytoskelet 33:241–251

    CAS  Google Scholar 

  108. Yoshida K, Soldati T (2006) Dissection of amoeboid movement into two mechanically distinct modes. J Cell Sci 119:3833–3844

    PubMed  CAS  Google Scholar 

  109. Friedl P, Wolf K (2010) Plasticity of cell migration: a multiscale tuning model. J Cell Biol 188:11–19

    PubMed Central  PubMed  CAS  Google Scholar 

  110. Sahai E, Marshall CJ (2003) Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. Nat Cell Biol 5:711–719

    PubMed  CAS  Google Scholar 

  111. Lammermann T, Bader BL, Monkley SJ, Worbs T, Wedlich-Soldner R, Hirsch K, Keller M, Forster R, Critchley DR, Fassler R, Sixt M (2008) Rapid leukocyte migration by integrin-independent flowing and squeezing. Nature 453:51–55

    PubMed  Google Scholar 

  112. Pinner S, Sahai E (2008) PDK1 regulates cancer cell motility by antagonising inhibition of ROCK1 by RhoE. Nat Cell Biol 10:127–137

    PubMed  CAS  Google Scholar 

  113. Eisenmann KM, Harris ES, Kitchen SM, Holman HA, Higgs HN, Alberts AS (2007) Dia-interacting protein modulates formin-mediated actin assembly at the cell cortex. Curr Biol 17:579–591

    PubMed  CAS  Google Scholar 

  114. Rabodzey A, Alcaide P, Luscinskas FW, Ladoux B (2008) Mechanical forces induced by the transendothelial migration of human neutrophils. Biophys J 95:1428–1438

    PubMed Central  PubMed  CAS  Google Scholar 

  115. Sabeh F, Shimizu-Hirota R, Weiss SJ (2009) Protease-dependent versus -independent cancer cell invasion programs: three-dimensional amoeboid movement revisited. J Cell Biol 185:11–19

    PubMed Central  PubMed  CAS  Google Scholar 

  116. Wolf K, Wu YI, Liu Y, Geiger J, Tam E, Overall C, Stack MS, Friedl P (2007) Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. Nat Cell Biol 9:893–904

    PubMed  CAS  Google Scholar 

  117. Gadea G, Sanz-Moreno V, Self A, Godi A, Marshall CJ (2008) DOCK10-mediated Cdc42 activation is necessary for amoeboid invasion of melanoma cells. Curr Biol 18:1456–1465

    PubMed  CAS  Google Scholar 

  118. Lorentzen A, Bamber J, Sadok A, Elson-Schwab I, Marshall CJ (2011) An ezrin-rich, rigid uropod-like structure directs movement of amoeboid blebbing cells. J Cell Sci 124:1256–1267

    PubMed  CAS  Google Scholar 

  119. Friedl P, Hegerfeldt Y, Tusch M (2004) Collective cell migration in morphogenesis and cancer. Int J Dev Biol 48:441–449

    PubMed  CAS  Google Scholar 

  120. Friedl P, Noble PB, Walton PA, Laird DW, Chauvin PJ, Tabah RJ, Black M, Zanker KS (1995) Migration of coordinated cell clusters in mesenchymal and epithelial cancer explants in vitro. Cancer Res 55:4557–4560

    PubMed  CAS  Google Scholar 

  121. Friedl P, Gilmour D (2009) Collective cell migration in morphogenesis, regeneration and cancer. Nat Rev Mol Cell Biol 10:445–457

    PubMed  CAS  Google Scholar 

  122. Garcia GL, Rericha EC, Heger CD, Goldsmith PK, Parent CA (2009) The group migration of Dictyostelium cells is regulated by extracellular chemoattractant degradation. Mol Biol Cell 20:3295–3304

    PubMed Central  PubMed  CAS  Google Scholar 

  123. Rieger S, Senghaas N, Walch A, Koster RW (2009) Cadherin-2 controls directional chain migration of cerebellar granule neurons. PLoS Biol 7:e1000240

    PubMed Central  PubMed  Google Scholar 

  124. Parri M, Chiarugi P (2010) Rac and Rho GTPases in cancer cell motility control. Cell Commun Signal 8:23

    PubMed Central  PubMed  Google Scholar 

  125. Ewald AJ, Brenot A, Duong M, Chan BS, Werb Z (2008) Collective epithelial migration and cell rearrangements drive mammary branching morphogenesis. Dev Cell 14:570–581

    PubMed Central  PubMed  CAS  Google Scholar 

  126. Gray RS, Cheung KJ, Ewald AJ (2010) Cellular mechanisms regulating epithelial morphogenesis and cancer invasion. Curr Opin Cell Biol 22:640–650

    PubMed Central  PubMed  CAS  Google Scholar 

  127. Scholl FG, Gamallo C, Vilaro S, Quintanilla M (1999) Identification of PA2.26 antigen as a novel cell-surface mucin-type glycoprotein that induces plasma membrane extensions and increased motility in keratinocytes. J Cell Sci 112(Pt 24):4601–4613

    PubMed  CAS  Google Scholar 

  128. Wicki A, Lehembre F, Wick N, Hantusch B, Kerjaschki D, Christofori G (2006) Tumor invasion in the absence of epithelial–mesenchymal transition: podoplanin-mediated remodeling of the actin cytoskeleton. Cancer Cell 9:261–272

    PubMed  CAS  Google Scholar 

  129. Hidalgo-Carcedo C, Hooper S, Chaudhry SI, Williamson P, Harrington K, Leitinger B, Sahai E (2011) Collective cell migration requires suppression of actomyosin at cell–cell contacts mediated by DDR1 and the cell polarity regulators Par3 and Par6. Nat Cell Biol 13:49–58

    PubMed Central  PubMed  CAS  Google Scholar 

  130. Levayer R, Pelissier-Monier A, Lecuit T (2011) Spatial regulation of Dia and Myosin-II by RhoGEF2 controls initiation of E-cadherin endocytosis during epithelial morphogenesis. Nat Cell Biol 13:529–540

    PubMed  CAS  Google Scholar 

  131. Shintani Y, Fukumoto Y, Chaika N, Svoboda R, Wheelock MJ, Johnson KR (2008) Collagen I-mediated up-regulation of N-cadherin requires cooperative signals from integrins and discoidin domain receptor 1. J Cell Biol 180:1277–1289

    PubMed Central  PubMed  CAS  Google Scholar 

  132. Theveneau E, Marchant L, Kuriyama S, Gull M, Moepps B, Parsons M, Mayor R (2010) Collective chemotaxis requires contact-dependent cell polarity. Dev Cell 19:39–53

    PubMed Central  PubMed  CAS  Google Scholar 

  133. Theveneau E, Mayor R (2010) Integrating chemotaxis and contact-inhibition during collective cell migration: small GTPases at work. Small GTPases 1:113–117

    PubMed Central  PubMed  Google Scholar 

  134. Poujade M, Grasland-Mongrain E, Hertzog A, Jouanneau J, Chavrier P, Ladoux B, Buguin A, Silberzan P (2007) Collective migration of an epithelial monolayer in response to a model wound. Proc Natl Acad Sci USA 104:15988–15993

    PubMed Central  PubMed  CAS  Google Scholar 

  135. Gaggioli C, Hooper S, Hidalgo-Carcedo C, Grosse R, Marshall JF, Harrington K, Sahai E (2007) Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. Nat Cell Biol 9:1392–1400

    PubMed  CAS  Google Scholar 

  136. Sanz-Moreno V, Gaggioli C, Yeo M, Albrengues J, Wallberg F, Viros A, Hooper S, Mitter R, Feral CC, Cook M, Larkin J, Marais R, Meneguzzi G, Sahai E, Marshall CJ (2011) ROCK and JAK1 signaling cooperate to control actomyosin contractility in tumor cells and stroma. Cancer Cell 20:229–245

    PubMed  CAS  Google Scholar 

  137. Rakic P (1972) Mode of cell migration to the superficial layers of fetal monkey neocortex. J Comp Neurol 145:61–83

    PubMed  CAS  Google Scholar 

  138. Kawauchi T, Sekine K, Shikanai M, Chihama K, Tomita K, Kubo K, Nakajima K, Nabeshima Y, Hoshino M (2010) Rab GTPases-dependent endocytic pathways regulate neuronal migration and maturation through N-cadherin trafficking. Neuron 67:588–602

    PubMed  CAS  Google Scholar 

  139. Shikanai M, Nakajima K, Kawauchi T (2011) N-cadherin regulates radial glial fiber-dependent migration of cortical locomoting neurons. Commun Integr Biol 4:326–330

    PubMed Central  PubMed  Google Scholar 

  140. Kalluri R (2009) EMT: when epithelial cells decide to become mesenchymal-like cells. J Clin Invest 119:1417–1419

    PubMed Central  PubMed  CAS  Google Scholar 

  141. Spaderna S, Schmalhofer O, Wahlbuhl M, Dimmler A, Bauer K, Sultan A, Hlubek F, Jung A, Strand D, Eger A, Kirchner T, Behrens J, Brabletz T (2008) The transcriptional repressor ZEB1 promotes metastasis and loss of cell polarity in cancer. Cancer Res 68:537–544

    PubMed  CAS  Google Scholar 

  142. Yang J, Mani SA, Donaher JL, Ramaswamy S, Itzykson RA, Come C, Savagner P, Gitelman I, Richardson A, Weinberg RA (2004) Twist, a master regulator of morphogenesis, plays an essential role in tumor metastasis. Cell 117:927–939

    PubMed  CAS  Google Scholar 

  143. Thiery JP, Acloque H, Huang RY, Nieto MA (2009) Epithelial–mesenchymal transitions in development and disease. Cell 139:871–890

    PubMed  CAS  Google Scholar 

  144. Radisky DC, Levy DD, Littlepage LE, Liu H, Nelson CM, Fata JE, Leake D, Godden EL, Albertson DG, Nieto MA, Werb Z, Bissell MJ (2005) Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. Nature 436:123–127

    PubMed Central  PubMed  CAS  Google Scholar 

  145. Hordijk PL, ten Klooster JP, van der Kammen RA, Michiels F, Oomen LC, Collard JG (1997) Inhibition of invasion of epithelial cells by Tiam1-Rac signaling. Science 278:1464–1466

    PubMed  CAS  Google Scholar 

  146. Malliri A, van Es S, Huveneers S, Collard JG (2004) The Rac exchange factor Tiam1 is required for the establishment and maintenance of cadherin-based adhesions. J Biol Chem 279:30092–30098

    PubMed  CAS  Google Scholar 

  147. Ahn J, Sanz-Moreno V, Marshall CJ (2012) The metastasis gene NEDD9 product acts through integrin beta3 and Src to promote mesenchymal motility and inhibit amoeboid motility. J Cell Sci 125:1814–1826

    PubMed  CAS  Google Scholar 

  148. Parri M, Taddei ML, Bianchini F, Calorini L, Chiarugi P (2009) EphA2 reexpression prompts invasion of melanoma cells shifting from mesenchymal to amoeboid-like motility style. Cancer Res 69:2072–2081

    PubMed  CAS  Google Scholar 

  149. Yamazaki D, Kurisu S, Takenawa T (2009) Involvement of Rac and Rho signaling in cancer cell motility in 3D substrates. Oncogene 28:1570–1583

    PubMed  CAS  Google Scholar 

  150. Palamidessi A, Frittoli E, Garre M, Faretta M, Mione M, Testa I, Diaspro A, Lanzetti L, Scita G, Di Fiore PP (2008) Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration. Cell 134:135–147

    PubMed  CAS  Google Scholar 

  151. Sahai E, Garcia-Medina R, Pouyssegur J, Vial E (2007) Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility. J Cell Biol 176:35–42

    PubMed Central  PubMed  CAS  Google Scholar 

  152. Oberoi TK, Dogan T, Hocking JC, Scholz RP, Mooz J, Anderson CL, Karreman C, Meyer zu Heringdorf D, Schmidt G, Ruonala M, Namikawa K, Harms GS, Carpy A, Macek B, Koster RW, Rajalingam K (2012) IAPs regulate the plasticity of cell migration by directly targeting Rac1 for degradation. Embo J 31:14–28

    PubMed Central  PubMed  CAS  Google Scholar 

  153. Oberoi-Khanuja TK, Rajalingam K (2012) IAPs as E3 ligases of Rac1: shaping the move. Small GTPases 3:131–136

    PubMed Central  PubMed  Google Scholar 

  154. Muller PA, Caswell PT, Doyle B, Iwanicki MP, Tan EH, Karim S, Lukashchuk N, Gillespie DA, Ludwig RL, Gosselin P, Cromer A, Brugge JS, Sansom OJ, Norman JC, Vousden KH (2009) Mutant p53 drives invasion by promoting integrin recycling. Cell 139:1327–1341

    PubMed  Google Scholar 

  155. Curmi PA, Gavet O, Charbaut E, Ozon S, Lachkar-Colmerauer S, Manceau V, Siavoshian S, Maucuer A, Sobel A (1999) Stathmin and its phosphoprotein family: general properties, biochemical and functional interaction with tubulin. Cell Struct Funct 24:345–357

    PubMed  CAS  Google Scholar 

  156. Belletti B, Nicoloso MS, Schiappacassi M, Berton S, Lovat F, Wolf K, Canzonieri V, D’Andrea S, Zucchetto A, Friedl P, Colombatti A, Baldassarre G (2008) Stathmin activity influences sarcoma cell shape, motility, and metastatic potential. Mol Biol Cell 19:2003–2013

    PubMed Central  PubMed  CAS  Google Scholar 

  157. Li N, Jiang P, Du W, Wu Z, Li C, Qiao M, Yang X, Wu M (2011) Siva1 suppresses epithelial-mesenchymal transition and metastasis of tumor cells by inhibiting stathmin and stabilizing microtubules. Proc Natl Acad Sci USA 108:12851–12856

    PubMed Central  PubMed  CAS  Google Scholar 

  158. Belletti B, Baldassarre G (2011) Stathmin: a protein with many tasks. New biomarker and potential target in cancer. Expert Opin Ther Targets 15:1249–1266

    PubMed  CAS  Google Scholar 

  159. Wolf K, Mazo I, Leung H, Engelke K, von Andrian UH, Deryugina EI, Strongin AY, Brocker EB, Friedl P (2003) Compensation mechanism in tumor cell migration: mesenchymal–amoeboid transition after blocking of pericellular proteolysis. J Cell Biol 160:267–277

    PubMed Central  PubMed  CAS  Google Scholar 

  160. Friedl P (2004) Prespecification and plasticity: shifting mechanisms of cell migration. Curr Opin Cell Biol 16:14–23

    PubMed  CAS  Google Scholar 

  161. Belgiovine C, Frapolli R, Bonezzi K, Chiodi I, Favero F, Mello-Grand M, Dei Tos AP, Giulotto E, Taraboletti G, D’Incalci M, Mondello C (2010) Reduced expression of the ROCK inhibitor Rnd3 is associated with increased invasiveness and metastatic potential in mesenchymal tumor cells. PLoS ONE 5:e14154

    PubMed Central  PubMed  CAS  Google Scholar 

  162. Grise F, Sena S, Bidaud-Meynard A, Baud J, Hiriart JB, Makki K, Dugot-Senant N, Staedel C, Bioulac-Sage P, Zucman-Rossi J, Rosenbaum J, Moreau V (2012) Rnd3/RhoE Is down-regulated in hepatocellular carcinoma and controls cellular invasion. Hepatology 55:1766–1775

    PubMed  CAS  Google Scholar 

  163. Luo H, Dong Z, Zou J, Zeng Q, Wu D, Liu L (2012) Down-regulation of RhoE is associated with progression and poor prognosis in hepatocellular carcinoma. J Surg Oncol 105:699–704

    PubMed  CAS  Google Scholar 

  164. Zhou J, Li K, Gu Y, Feng B, Ren G, Zhang L, Wang Y, Nie Y, Fan D (2011) Transcriptional up-regulation of RhoE by hypoxia-inducible factor (HIF)-1 promotes epithelial to mesenchymal transition of gastric cancer cells during hypoxia. Biochem Biophys Res Commun 415:348–354

    PubMed  CAS  Google Scholar 

  165. Petrie RJ, Gavara N, Chadwick RS, Yamada KM (2012) Nonpolarized signaling reveals two distinct modes of 3D cell migration. J Cell Biol 197:439–455

    PubMed Central  PubMed  CAS  Google Scholar 

  166. Friedl P, Alexander S (2011) Cancer invasion and the microenvironment: plasticity and reciprocity. Cell 147:992–1009

    PubMed  CAS  Google Scholar 

  167. Hegerfeldt Y, Tusch M, Brocker EB, Friedl P (2002) Collective cell movement in primary melanoma explants: plasticity of cell–cell interaction, beta1-integrin function, and migration strategies. Cancer Res 62:2125–2130

    PubMed  CAS  Google Scholar 

  168. Wyckoff J, Wang W, Lin EY, Wang Y, Pixley F, Stanley ER, Graf T, Pollard JW, Segall J, Condeelis J (2004) A paracrine loop between tumor cells and macrophages is required for tumor cell migration in mammary tumors. Cancer Res 64:7022–7029

    PubMed  CAS  Google Scholar 

  169. Zhao J, Mialki RK, Wei J, Coon TA, Zou C, Chen BB, Mallampalli RK, Zhao Y (2013) SCF E3 ligase F-box protein complex SCF(FBXL19) regulates cell migration by mediating Rac1 ubiquitination and degradation. Faseb J 27:2611–2619

    PubMed  CAS  Google Scholar 

  170. Flatau G, Lemichez E, Gauthier M, Chardin P, Paris S, Fiorentini C, Boquet P (1997) Toxin-induced activation of the G protein p21 Rho by deamidation of glutamine. Nature 387:729–733

    PubMed  CAS  Google Scholar 

  171. Schmidt G, Sehr P, Wilm M, Selzer J, Mann M, Aktories K (1997) Gln 63 of Rho is deamidated by Escherichia coli cytotoxic necrotizing factor-1. Nature 387:725–729

    PubMed  CAS  Google Scholar 

  172. Lerm M, Pop M, Fritz G, Aktories K, Schmidt G (2002) Proteasomal degradation of cytotoxic necrotizing factor 1-activated rac. Infect Immun 70:4053–4058

    PubMed Central  PubMed  CAS  Google Scholar 

  173. Ozdamar B, Bose R, Barrios-Rodiles M, Wang HR, Zhang Y, Wrana JL (2005) Regulation of the polarity protein Par6 by TGFbeta receptors controls epithelial cell plasticity. Science 307:1603–1609

    PubMed  CAS  Google Scholar 

  174. Wang HR, Zhang Y, Ozdamar B, Ogunjimi AA, Alexandrova E, Thomsen GH, Wrana JL (2003) Regulation of cell polarity and protrusion formation by targeting RhoA for degradation. Science 302:1775–1779

    PubMed  CAS  Google Scholar 

  175. Bryan B, Cai Y, Wrighton K, Wu G, Feng XH, Liu M (2005) Ubiquitination of RhoA by Smurf1 promotes neurite outgrowth. FEBS Lett 579:1015–1019

    PubMed  CAS  Google Scholar 

  176. Zimmerman ES, Schulman BA, Zheng N (2010) Structural assembly of cullin-RING ubiquitin ligase complexes. Curr Opin Struct Biol 20:714–721

    PubMed Central  PubMed  CAS  Google Scholar 

  177. Chen Y, Yang Z, Meng M, Zhao Y, Dong N, Yan H, Liu L, Ding M, Peng HB, Shao F (2009) Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement. Mol Cell 35:841–855

    PubMed  CAS  Google Scholar 

  178. Wei J, Mialki RK, Dong S, Khoo A, Mallampalli RK, Zhao Y, Zhao J (2013) A new mechanism of RhoA ubiquitination and degradation: roles of SCF E3 ligase and Erk2. Biochim Biophys Acta 1833:2757–2764

    PubMed  CAS  Google Scholar 

  179. Torrino S, Visvikis O, Doye A, Boyer L, Stefani C, Munro P, Bertoglio J, Gacon G, Mettouchi A, Lemichez E (2011) The E3 ubiquitin-ligase HACE1 catalyzes the ubiquitylation of active Rac1. Dev Cell 21:959–965

    PubMed  CAS  Google Scholar 

  180. Castillo-Lluva S, Tatham MH, Jones RC, Jaffray EG, Edmondson RD, Hay RT, Malliri A (2010) SUMOylation of the GTPase Rac1 is required for optimal cell migration. Nat Cell Biol 12:1078–1085

    PubMed Central  PubMed  CAS  Google Scholar 

  181. Yu J, Zhang D, Liu J, Li J, Yu Y, Wu XR, Huang C (2012) RhoGDI SUMOylation at Lys-138 increases its binding activity to Rho GTPase and its inhibiting cancer cell motility. J Biol Chem 287:13752–13760

    PubMed Central  PubMed  CAS  Google Scholar 

  182. Liu J, Zhang D, Luo W, Yu Y, Yu J, Li J, Zhang X, Zhang B, Chen J, Wu XR, Rosas-Acosta G, Huang C (2011) X-linked inhibitor of apoptosis protein (XIAP) mediates cancer cell motility via Rho GDP dissociation inhibitor (RhoGDI)-dependent regulation of the cytoskeleton. J Biol Chem 286:15630–15640

    PubMed Central  PubMed  CAS  Google Scholar 

  183. DerMardirossian C, Bokoch GM (2005) GDIs: central regulatory molecules in Rho GTPase activation. Trends Cell Biol 15:356–363

    PubMed  CAS  Google Scholar 

  184. Fukumoto Y, Kaibuchi K, Hori Y, Fujioka H, Araki S, Ueda T, Kikuchi A, Takai Y (1990) Molecular cloning and characterization of a novel type of regulatory protein (GDI) for the rho proteins, ras p21-like small GTP-binding proteins. Oncogene 5:1321–1328

    PubMed  CAS  Google Scholar 

  185. Leonard D, Hart MJ, Platko JV, Eva A, Henzel W, Evans T, Cerione RA (1992) The identification and characterization of a GDP-dissociation inhibitor (GDI) for the CDC42Hs protein. J Biol Chem 267:22860–22868

    PubMed  CAS  Google Scholar 

  186. Boulter E, Garcia-Mata R, Guilluy C, Dubash A, Rossi G, Brennwald PJ, Burridge K (2010) Regulation of Rho GTPase crosstalk, degradation and activity by RhoGDI1. Nat Cell Biol 12:477–483

    PubMed Central  PubMed  CAS  Google Scholar 

  187. Bielek H, Anselmo A, Dermardirossian C (2009) Morphological and proliferative abnormalities in renal mesangial cells lacking RhoGDI. Cell Signal 21:1974–1983

    PubMed Central  PubMed  CAS  Google Scholar 

  188. Liu M, Bi F, Zhou X, Zheng Y (2012) Rho GTPase regulation by miRNAs and covalent modifications. Trends Cell Biol 22:365–373

    PubMed Central  PubMed  CAS  Google Scholar 

  189. Ispanovic E, Serio D, Haas TL (2008) Cdc42 and RhoA have opposing roles in regulating membrane type 1-matrix metalloproteinase localization and matrix metalloproteinase-2 activation. Am J Physiol Cell Physiol 295:C600–C610

    PubMed  CAS  Google Scholar 

  190. Saito K, Ozawa Y, Hibino K, Ohta Y (2012) FilGAP, a Rho/Rho-associated protein kinase-regulated GTPase-activating protein for Rac, controls tumor cell migration. Mol Biol Cell 23:4739–4750

    Google Scholar 

  191. Noguchi F, Inui S, Nakajima T, Itami S (2012) Hic-5 affects proliferation, migration and invasion of B16 murine melanoma cells. Pigment Cell Melanoma Res 25:773–782

    PubMed  CAS  Google Scholar 

  192. Taddei ML, Parri M, Angelucci A, Bianchini F, Marconi C, Giannoni E, Raugei G, Bologna M, Calorini L, Chiarugi P (2011) EphA2 induces metastatic growth regulating amoeboid motility and clonogenic potential in prostate carcinoma cells. Mol Cancer Res 9:149–160

    PubMed  CAS  Google Scholar 

  193. Kitzing TM, Wang Y, Pertz O, Copeland JW, Grosse R (2010) Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC. Oncogene 29:2441–2448

    PubMed  CAS  Google Scholar 

  194. Omelchenko T, Hall A (2012) Myosin-IXA regulates collective epithelial cell migration by targeting RhoGAP activity to cell–cell junctions. Curr Biol 22:278–288

    PubMed Central  PubMed  CAS  Google Scholar 

  195. Letunic I, Bork P (2007) Interactive Tree Of Life (iTOL): an online tool for phylogenetic tree display and annotation. Bioinformatics 23:127–128

    PubMed  CAS  Google Scholar 

Download references

Acknowledgments

The work in KR’s lab was funded through ENP programme grant RA1739/1-1 from the DFG and a PLUS3 grant from Boehringer Ingelheim Stiftung to KR. We apologize to colleagues whose work could not be cited due to space constraints.

Author information

Authors and Affiliations

  1. Cell Death Signaling Group, Institute of Biochemistry II, Goethe University Medical School, Frankfurt, Germany

    Arun Murali & Krishnaraj Rajalingam

Authors
  1. Arun Murali
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Krishnaraj Rajalingam
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Krishnaraj Rajalingam.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Murali, A., Rajalingam, K. Small Rho GTPases in the control of cell shape and mobility. Cell. Mol. Life Sci. 71, 1703–1721 (2014). https://doi.org/10.1007/s00018-013-1519-6

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s00018-013-1519-6

Keywords

Search

Navigation