Rac and Rho GTPases in cancer cell motility control

Cell Communication and Signaling

Volumn 8, Issue , 2010, Pages

  Parri, Matteo ^a   Chiarugi, Paola ^b  

^a Externautics R and D   (Italy)

^b UNIVERSITY OF FLORENCE   (Italy)

Author keywords

[No Author keywords available]

Indexed keywords

EID: 77956459044     PISSN: None     EISSN: 1478811X     Source Type: Journal    
DOI: 10.1186/1478-811X-8-23     Document Type: Review

References (152)

1. Rho GTPases in cell biology. S Etienne-Manneville, A Hall, Nature 2002 420 629 635 10.1038/nature01148 12478284
2. Rho GTPases and actin dynamics in membrane protrusions and vesicle trafficking. AJ Ridley, Trends Cell Biol 2006 16 522 529 10.1016/j.tcb.2006.08. 006 16949823
3. The ras protein family: evolutionary tree and role of conserved amino acids. A Valencia, P Chardin, A Wittinghofer, C Sander, Biochemistry 1991 30 4637 4648 10.1021/bi00233a001 2029511
4. Rac1 GTPase: a "Rac" of all trades. EE Bosco, JC Mulloy, Y Zheng, Cell Mol Life Sci 2009 66 370 374 10.1007/s00018-008-8552-x 19151919
5. GEF what? Dock180 and related proteins help Rac to polarize cells in new ways. JF Cote, K Vuori, Trends Cell Biol 2007 17 383 393 10.1016/j.tcb.2007.05. 001 17765544
6. Guanine nucleotide exchange factors for Rho GTPases: turning on the switch. A Schmidt, A Hall, Genes Dev 2002 16 1587 1609 10.1101/gad.1003302 12101119
7. Hydrophobic modifications of Ras proteins by isoprenoid groups and fatty acids - More than just membrane anchoring. M Pechlivanis, J Kuhlmann, Biochim Biophys Acta 2006 1764 1914 1931 17110180
8. Serine phosphorylation negatively regulates RhoA in vivo. SM Ellerbroek, K Wennerberg, K Burridge, J Biol Chem 2003 278 19023 19031 10.1074/jbc. M213066200 12654918
9. Function and regulation of Rnd proteins. P Chardin, Nat Rev Mol Cell Biol 2006 7 54 62 10.1038/nrm1788 16493413
10. The hematopoiesis-specific GTP-binding protein RhoH is GTPase deficient and modulates activities of other Rho GTPases by an inhibitory function. X Li, X Bu, B Lu, H Avraham, RA Flavell, B Lim, Mol Cell Biol 2002 22 1158 1171 10.1128/MCB.22.4.1158-1171.2002 11809807
11. Lysosomal degradation of RhoH protein upon antigen receptor activation in T but not B cells. J Schmidt-Mende, B Geering, S Yousefi, HU Simon, Eur J Immunol 2010 40 525 529 10.1002/eji.200939556 19950172
12. GDIs: central regulatory molecules in Rho GTPase activation. C DerMardirossian, GM Bokoch, Trends Cell Biol 2005 15 356 363 10.1016/j.tcb.2005.05.001 15921909
13. Rho GTPase-activating proteins in cell regulation. SY Moon, Y Zheng, Trends Cell Biol 2003 13 13 22 10.1016/S0962-8924(02)00004-1 12480336
14. Mechanism of regulation of WAVE1-induced actin nucleation by Rac1 and Nck. S Eden, R Rohatgi, AV Podtelejnikov, M Mann, MW Kirschner, Nature 2002 418 790 793 10.1038/nature00859 12181570
15. Alternative splicing of Rac1 generates Rac1b, a self-activating GTPase. D Fiegen, LC Haeusler, L Blumenstein, U Herbrand, R Dvorsky, IR Vetter, MR Ahmadian, J Biol Chem 2004 279 4743 4749 10.1074/jbc.M310281200 14625275
16. Tumor-related alternatively spliced Rac1b is not regulated by Rho-GDP dissociation inhibitors and exhibits selective downstream signaling. P Matos, JG Collard, P Jordan, J Biol Chem 2003 278 50442 50448 10.1074/jbc.M308215200 14506233
17. Akt protein kinase inhibits Rac1-GTP binding through phosphorylation at serine 71 of Rac1. T Kwon, DY Kwon, J Chun, JH Kim, SS Kang, J Biol Chem 2000 275 423 428 10.1074/jbc.275.1.423 10617634
18. rac, a novel ras-related family of proteins that are botulinum toxin substrates. J Didsbury, RF Weber, GM Bokoch, T Evans, R Snyderman, J Biol Chem 1989 264 16378 16382 2674130
19. Human neutrophil immunodeficiency syndrome is associated with an inhibitory Rac2 mutation. DR Ambruso, C Knall, AN Abell, J Panepinto, A Kurkchubasche, G Thurman, C Gonzalez-Aller, A Hiester, M deBoer, RJ Harbeck, R Oyer, GL Johnson, D Roos, Proc Natl Acad Sci USA 2000 97 4654 4659 10.1073/pnas.080074897 10758162
20. GTPases and reactive oxygen species: switches for killing and signaling. E Werner, J Cell Sci 2004 117 143 153 10.1242/jcs.00937 14676270
21. Characterization of RAC3, a novel member of the Rho family. L Haataja, J Groffen, N Heisterkamp, J Biol Chem 1997 272 20384 20388 10.1074/jbc.272.33. 20384 9252344
22. Endogenous, hyperactive Rac3 controls proliferation of breast cancer cells by a p21-activated kinase-dependent pathway. JP Mira, V Benard, J Groffen, LC Sanders, UG Knaus, Proc Natl Acad Sci USA 2000 97 185 189 10.1073/pnas.97.1.185 10618392
23. Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. AP Wheeler, AJ Ridley, Exp Cell Res 2004 301 43 49 10.1016/j.yexcr.2004.08.012 15501444
24. Rho GTPases and the actin cytoskeleton. A Hall, Science 1998 279 509 514 10.1126/science.279.5350.509 9438836
25. Rho GTPases and signaling networks. AL Van, C D'Souza-Schorey, Genes Dev 1997 11 2295 2322 10.1101/gad.11.18.2295 9308960
26. Cell migration: a physically integrated molecular process. DA Lauffenburger, AF Horwitz, Cell 1996 84 359 369 10.1016/S0092-8674(00)81280-5 8608589
27. Molecular mechanisms controlling actin filament dynamics in nonmuscle cells. TD Pollard, L Blanchoin, RD Mullins, Annu Rev Biophys Biomol Struct 2000 29 545 576 10.1146/annurev.biophys.29.1.545 10940259
28. Electron tomography reveals unbranched networks of actin filaments in lamellipodia. E Urban, S Jacob, M Nemethova, GP Resch, JV Small, Nat Cell Biol 2010 12 429 435 10.1038/ncb2044 20418872
29. A nucleator arms race: cellular control of actin assembly. KG Campellone, MD Welch, Nat Rev Mol Cell Biol 2010 11 237 251 10.1038/nrm2867 20237478
30. Actin nucleation and elongation factors: mechanisms and interplay. MA Chesarone, BL Goode, Curr Opin Cell Biol 2009 21 28 37 10.1016/j.ceb.2008.12.001 19168341
31. IRSp53 is an essential intermediate between Rac and WAVE in the regulation of membrane ruffling. H Miki, H Yamaguchi, S Suetsugu, T Takenawa, Nature 2000 408 732 735 10.1038/35047107 11130076
32. Visualizing muscle cell migration in situ. B Knight, C Laukaitis, N Akhtar, NA Hotchin, M Edlund, AR Horwitz, Curr Biol 2000 10 576 585 10.1016/S0960-9822(00)00486-3 10837222
33. Activation of cdc42, rac, PAK, and rho-kinase in response to hepatocyte growth factor differentially regulates epithelial cell colony spreading and dissociation. I Royal, N Lamarche-Vane, L Lamorte, K Kaibuchi, M Park, Mol Biol Cell 2000 11 1709 1725 10793146
34. Regulation of the cytoskeleton and cell adhesion by the Rho family GTPases in mammalian cells. K Kaibuchi, S Kuroda, M Amano, Annu Rev Biochem 1999 68 459 486 10.1146/annurev.biochem.68.1.459 10872457
35. Unconventional myosins in cell movement, membrane traffic, and signal transduction. V Mermall, PL Post, MS Mooseker, Science 1998 279 527 533 10.1126/science.279.5350.527 9438839
36. Specific localization of serine 19 phosphorylated myosin II during cell locomotion and mitosis of cultured cells. F Matsumura, S Ono, Y Yamakita, G Totsukawa, S Yamashiro, J Cell Biol 1998 140 119 129 10.1083/jcb.140.1.119 9425160
37. Rac regulates phosphorylation of the myosin-II heavy chain, actinomyosin disassembly and cell spreading. FN van Leeuwen, DS van, HE Kain, RA van der Kammen, JG Collard, Nat Cell Biol 1999 1 242 248 10.1038/12068 10559923
38. Rac recruits high-affinity integrin alphavbeta3 to lamellipodia in endothelial cell migration. WB Kiosses, SJ Shattil, N Pampori, MA Schwartz, Nat Cell Biol 2001 3 316 320 10.1038/35060120 11231584
39. Dynamics and segregation of cell-matrix adhesions in cultured fibroblasts. E Zamir, M Katz, Y Posen, N Erez, KM Yamada, BZ Katz, S Lin, DC Lin, A Bershadsky, Z Kam, B Geiger, Nat Cell Biol 2000 2 191 196 10.1038/35008607 10783236
40. Molecular complexity and dynamics of cell-matrix adhesions. E Zamir, B Geiger, J Cell Sci 2001 114 3583 3590 11707510
41. Interplay between Rac and Rho in the control of substrate contact dynamics. K Rottner, A Hall, JV Small, Curr Biol 1999 9 640 648 10.1016/S0960-9822(99)80286-3 10375527
42. Activation of Rac and Cdc42 by integrins mediates cell spreading. LS Price, J Leng, MA Schwartz, GM Bokoch, Mol Biol Cell 1998 9 1863 1871 9658176
43. Proteolysis and cell migration: creating a path? G Murphy, J Gavrilovic, Curr Opin Cell Biol 1999 11 614 621 10.1016/S0955-0674(99)00022-8 10508651
44. Biomechanical regulation of matrix metalloproteinase-9 in cultured chondrocytes. G Jin, RL Sah, YS Li, M Lotz, JY Shyy, S Chien, J Orthop Res 2000 18 899 908 10.1002/jor.1100180608 11192249
45. Role of Rac1 and oxygen radicals in collagenase-1 expression induced by cell shape change. F Kheradmand, E Werner, P Tremble, M Symons, Z Werb, Science 1998 280 898 902 10.1126/science.280.5365.898 9572733
46. Regulation of matrix metalloproteinase expression in tumor invasion. J Westermarck, VM Kahari, FASEB J 1999 13 781 792 10224222
47. Rac1 mediates type I collagen-dependent MMP-2 activation. role in cell invasion across collagen barrier. Y Zhuge, J Xu, J Biol Chem 2001 276 16248 16256 11340084
48. Rho-Rho-kinase pathway in smooth muscle contraction and cytoskeletal reorganization of non-muscle cells. Y Fukata, M Amano, K Kaibuchi, Trends Pharmacol Sci 2001 22 32 39 10.1016/S0165-6147(00)01596-0 11165670
49. Distinct roles of ROCK (Rho-kinase) and MLCK in spatial regulation of MLC phosphorylation for assembly of stress fibers and focal adhesions in 3T3 fibroblasts. G Totsukawa, Y Yamakita, S Yamashiro, DJ Hartshorne, Y Sasaki, F Matsumura, J Cell Biol 2000 150 797 806 10.1083/jcb.150.4.797 10953004
50. Physical and biochemical regulation of integrin release during rear detachment of migrating cells. SP Palecek, A Huttenlocher, AF Horwitz, DA Lauffenburger, J Cell Sci 1998 111 Pt 7 929 940 9490637
51. Actin dynamics: assembly and disassembly of actin networks. MA Wear, DA Schafer, JA Cooper, Curr Biol 2000 10 891 R895 10.1016/S0960-9822(00)00845-9 11137023
52. Calpain regulates actin remodeling during cell spreading. DA Potter, JS Tirnauer, R Janssen, DE Croall, CN Hughes, KA Fiacco, JW Mier, M Maki, IM Herman, J Cell Biol 1998 141 647 662 10.1083/jcb.141.3.647 9566966
53. Regulation of integrin-mediated adhesion during cell migration. EA Cox, A Huttenlocher, Microsc Res Tech 1998 43 412 419 10.1002/(SICI)1097- 0029(19981201)43:5<412::AID-JEMT7>3.0.CO;2-F 9858338
54. Tumour-cell invasion and migration: diversity and escape mechanisms. P Friedl, K Wolf, Nat Rev Cancer 2003 3 362 374 10.1038/nrc1075 12724734
55. Prespecification and plasticity: shifting mechanisms of cell migration. P Friedl, Curr Opin Cell Biol 2004 16 14 23 10.1016/j.ceb.2003.11.001 15037300
56. Tenascin-C and SF/HGF produced by myofibroblasts in vitro provide convergent pro-invasive signals to human colon cancer cells through RhoA and Rac. WO De, QD Nguyen, HL Van, M Bracke, E Bruyneel, C Gespach, M Mareel, FASEB J 2004 18 1016 1018 15059978
57. Cell migration: integrating signals from front to back. AJ Ridley, MA Schwartz, K Burridge, RA Firtel, MH Ginsberg, G Borisy, JT Parsons, AR Horwitz, Science 2003 302 1704 1709 10.1126/science.1092053 14657486
58. Integrin-mediated activation of Cdc42 controls cell polarity in migrating astrocytes through PKCzeta. S Etienne-Manneville, A Hall, Cell 2001 106 489 498 10.1016/S0092-8674(01)00471-8 11525734
59. ERK-MAPK signaling coordinately regulates activity of Rac1 and RhoA for tumor cell motility. E Vial, E Sahai, CJ Marshall, Cancer Cell 2003 4 67 79 10.1016/S1535-6108(03)00162-4 12892714
60. Differing modes of tumour cell invasion have distinct requirements for Rho/ROCK signalling and extracellular proteolysis. E Sahai, CJ Marshall, Nat Cell Biol 2003 5 711 719 10.1038/ncb1019 12844144
61. The urokinase-type plasminogen activator system in cancer metastasis: a review. PA Andreasen, L Kjoller, L Christensen, MJ Duffy, Int J Cancer 1997 72 1 22 10.1002/(SICI)1097-0215(19970703)72:1<1::AID-IJC1>3.0.CO;2-Z 9212216
62. Matrix metalloproteinases in tumor invasion: role for cell migration. K Nabeshima, T Inoue, Y Shimao, T Sameshima, Pathol Int 2002 52 255 264 10.1046/j.1440-1827.2002.01343.x 12031080
63. Amoeboid leukocyte crawling through extracellular matrix: lessons from the Dictyostelium paradigm of cell movement. P Friedl, S Borgmann, EB Brocker, J Leukoc Biol 2001 70 491 509 11590185
64. A critical step in metastasis: in vivo analysis of intravasation at the primary tumor. JB Wyckoff, JG Jones, JS Condeelis, JE Segall, Cancer Res 2000 60 2504 2511 10811132
65. Plasticity of cell migration: a multiscale tuning model. P Friedl, K Wolf, J Cell Biol 2010 188 11 19 10.1083/jcb.200909003 19951899
66. Compensation mechanism in tumor cell migration: mesenchymal-amoeboid transition after blocking of pericellular proteolysis. K Wolf, I Mazo, H Leung, K Engelke, UH von Andrian, EI Deryugina, AY Strongin, EB Brocker, P Friedl, J Cell Biol 2003 160 267 277 10.1083/jcb.200209006 12527751
67. Tube travel: the role of proteases in individual and collective cancer cell invasion. P Friedl, K Wolf, Cancer Res 2008 68 7247 7249 10.1158/0008-5472.CAN-08-0784 18794108
68. Multi-step pericellular proteolysis controls the transition from individual to collective cancer cell invasion. K Wolf, YI Wu, Y Liu, J Geiger, E Tam, C Overall, MS Stack, P Friedl, Nat Cell Biol 2007 9 893 904 10.1038/ncb1616 17618273
69. Mechanisms of motility in metastasizing cells. M Yilmaz, G Christofori, Mol Cancer Res 2010 8 629 642 10.1158/1541-7786.MCR-10-0139 20460404
70. Fibroblasts in cancer. R Kalluri, M Zeisberg, Nat Rev Cancer 2006 6 392 401 10.1038/nrc1877 16572188
71. EMT: when epithelial cells decide to become mesenchymal-like cells. R Kalluri, J Clin Invest 2009 119 1417 1419 10.1172/JCI39675 19487817
72. Epithelial-mesenchymal transitions in tumour progression. JP Thiery, Nat Rev Cancer 2002 2 442 454 10.1038/nrc822 12189386
73. Matrix metalloproteinase stromelysin-1 triggers a cascade of molecular alterations that leads to stable epithelial-to-mesenchymal conversion and a premalignant phenotype in mammary epithelial cells. A Lochter, S Galosy, J Muschler, N Freedman, Z Werb, MJ Bissell, J Cell Biol 1997 139 1861 1872 10.1083/jcb.139.7.1861 9412478
74. Rac1b and reactive oxygen species mediate MMP-3-induced EMT and genomic instability. DC Radisky, DD Levy, LE Littlepage, H Liu, CM Nelson, JE Fata, D Leake, EL Godden, DG Albertson, MA Nieto, Z Werb, MJ Bissel, Nature 2005 436 123 127 10.1038/nature03688 16001073
75. Stabilization of snail by NF-kappaB is required for inflammation-induced cell migration and invasion. Y Wu, J Deng, PG Rychahou, S Qiu, BM Evers, BP Zhou, Cancer Cell 2009 15 416 428 10.1016/j.ccr.2009.03.016 19411070
76. A hypoxic twist in metastasis. H Peinado, A Cano, Nat Cell Biol 2008 10 253 254 10.1038/ncb0308-253 18311179
77. Direct regulation of TWIST by HIF-1alpha promotes metastasis. MH Yang, MZ Wu, SH Chiou, PM Chen, SY Chang, CJ Liu, SC Teng, KJ Wu, Nat Cell Biol 2008 10 295 305 10.1038/ncb1691 18297062
78. TWIST activation by hypoxia inducible factor-1 (HIF-1): implications in metastasis and development. MH Yang, KJ Wu, Cell Cycle 2008 7 2090 2096 10.4161/cc.7.14.6324 18635960
79. NF-kappaB represses E-cadherin expression and enhances epithelial to mesenchymal transition of mammary epithelial cells: potential involvement of ZEB-1 and ZEB-2. HL Chua, P Bhat-Nakshatri, SE Clare, A Morimiya, S Badve, H Nakshatri, Oncogene 2007 26 711 724 10.1038/sj.onc.1209808 16862183
80. miR-205 Exerts tumor-suppressive functions in human prostate through down-regulation of protein kinase Cepsilon. P Gandellini, M Folini, N Longoni, M Pennati, M Binda, M Colecchia, R Salvioni, R Supino, R Moretti, P Limonta, R Valdagni, MG Daidone, N Zaffaroni, Cancer Res 2009 69 2287 2295 10.1158/0008-5472.CAN-08-2894 19244118
81. EphA2 reexpression prompts invasion of melanoma cells shifting from mesenchymal to amoeboid-like motility style. M Parri, ML Taddei, F Bianchini, L Calorini, P Chiarugi, Cancer Res 2009 69 2072 2081 10.1158/0008-5472.CAN-08-1845 19244130
82. Calpain 2 and Src dependence distinguishes mesenchymal and amoeboid modes of tumour cell invasion: a link to integrin function. NO Carragher, SM Walker, LA Scott Carragher, F Harris, TK Sawyer, VG Brunton, BW Ozanne, MC Frame, Oncogene 2006 25 5726 5740 10.1038/sj.onc.1209582 16652152
83. EphrinA1 activates a Src/focal adhesion kinase-mediated motility response leading to rho-dependent actino/myosin contractility. M Parri, F Buricchi, E Giannoni, G Grimaldi, T Mello, G Raugei, G Ramponi, P Chiarugi, J Biol Chem 2007 282 19619 19628 10.1074/jbc.M701319200 17449913
84. Kinase-dependent and -independent roles of EphA2 in the regulation of prostate cancer invasion and metastasis. ML Taddei, M Parri, A Angelucci, B Onnis, F Bianchini, E Giannoni, G Raugei, L Calorini, N Rucci, A Teti, M Bologna, P Chiarugi, Am J Pathol 2009 174 1492 1503 10.2353/ajpath.2009.080473 19264906
85. Stathmin activity influences sarcoma cell shape, motility, and metastatic potential. B Belletti, MS Nicoloso, M Schiappacassi, S Berton, F Lovat, K Wolf, V Canzonieri, S D'Andrea, A Zucchetto, P Friedl, A Colombatti, G Baldassarre, Mol Biol Cell 2008 19 2003 2013 10.1091/mbc.E07-09-0894 18305103
86. Smurf1 regulates tumor cell plasticity and motility through degradation of RhoA leading to localized inhibition of contractility. E Sahai, R Garcia-Medina, J Pouyssegur, E Vial, J Cell Biol 2007 176 35 42 10.1083/jcb.200605135 17190792
87. p27kip1 controls cell morphology and motility by regulating microtubule-dependent lipid raft recycling. B Belletti, I Pellizzari, S Berton, L Fabris, K Wolf, F Lovat, M Schiappacassi, S D'Andrea, MS Nicoloso, S Lovisa, M Sonego, P Defilippi, A Vecchione, A Colombatti, P Friedl, G Baldassarre, Mol Cell Biol 2010 30 2229 2240 10.1128/MCB.00723-09 20194624
88. The tumor suppressor functions of p27(kip1) include control of the mesenchymal/amoeboid transition. S Berton, B Belletti, K Wolf, V Canzonieri, F Lovat, A Vecchione, A Colombatti, P Friedl, G Baldassarre, Mol Cell Biol 2009 29 5031 5045 10.1128/MCB.00144-09 19596789
89. Loss of p53 promotes RhoA-ROCK-dependent cell migration and invasion in 3 D matrices. G Gadea, TM de, C Anguille, P Roux, J Cell Biol 2007 178 23 30 10.1083/jcb.200701120 17606864
90. Collective cell migration in morphogenesis, regeneration and cancer. P Friedl, D Gilmour, Nat Rev Mol Cell Biol 2009 10 445 457 10.1038/nrm2720 19546857
91. Collective cell movement in primary melanoma explants: plasticity of cell-cell interaction, beta1-integrin function, and migration strategies. Y Hegerfeldt, M Tusch, EB Brocker, P Friedl, Cancer Res 2002 62 2125 2130 11929834
92. Rac activation and inactivation control plasticity of tumor cell movement. V Sanz-Moreno, G Gadea, J Ahn, H Paterson, P Marra, S Pinner, E Sahai, CJ Marshall, Cell 2008 135 510 523 10.1016/j.cell.2008.09.043 18984162
93. Endocytic trafficking of Rac is required for the spatial restriction of signaling in cell migration. A Palamidessi, E Frittoli, M Garre, M Faretta, M Mione, I Testa, A Diaspro, L Lanzetti, G Scita, PP Di Fiore, Cell 2008 134 135 147 10.1016/j.cell.2008.05.034 18614017
94. Redox-dependent downregulation of Rho by Rac. AS Nimnual, LJ Taylor, D Bar-Sagi, Nat Cell Biol 2003 5 236 241 10.1038/ncb938 12598902
95. The low M(r) protein-tyrosine phosphatase is involved in Rho-mediated cytoskeleton rearrangement after integrin and platelet-derived growth factor stimulation. P Chiarugi, P Cirri, L Taddei, E Giannoni, G Camici, G Manao, G Raugei, G Ramponi, J Biol Chem 2000 275 4640 4646 10.1074/jbc.275.7.4640 10671492
96. Redox regulation of ephrin/integrin cross-talk. F Buricchi, E Giannoni, G Grimaldi, M Parri, G Raugei, G Ramponi, P Chiarugi, Cell Adh Migr 2007 1 33 42 19262085
97. p120-catenin and p190RhoGAP regulate cell-cell adhesion by coordinating antagonism between Rac and Rho. GA Wildenberg, MR Dohn, RH Carnahan, MA Davis, NA Lobdell, J Settleman, AB Reynolds, Cell 2006 127 1027 1039 10.1016/j.cell.2006.09.046 17129786
98. Another job for the talented p120-catenin. CM Niessen, AS Yap, Cell 2006 127 875 877 10.1016/j.cell.2006.11.014 17129772
99. Ras and Rho GTPases: a family reunion. D Bar-Sagi, A Hall, Cell 2000 103 227 238 10.1016/S0092-8674(00)00115-X 11057896
100. Rho family proteins: coordinating cell responses. AJ Ridley, Trends Cell Biol 2001 11 471 477 10.1016/S0962-8924(01)02153-5 11719051
101. The role of Rho GTPases in disease development. B Boettner, AL Van, Gene 2002 286 155 174 10.1016/S0378-1119(02)00426-2 11943472
102. Rho GTPases: potential candidates for anticancer therapy. S Aznar, P Fernandez-Valeron, C Espina, JC Lacal, Cancer Lett 2004 206 181 191 10.1016/j.canlet.2003.08.035 15013523
103. RHO-GTPases and cancer. E Sahai, CJ Marshall, Nat Rev Cancer 2002 2 133 142 10.1038/nrc725 12635176
104. Rho GTPases in human cancer: an unresolved link to upstream and downstream transcriptional regulation. SA Benitah, PF Valeron, AL Van, CJ Marshall, JC Lacal, Biochim Biophys Acta 2004 1705 121 132 15588766
105. Multifaceted role of Rho proteins in angiogenesis. SD Merajver, SZ Usmani, J Mammary Gland Biol Neoplasia 2005 10 291 298 10.1007/s10911-006-9002-8 16900393
106. Rho GTPase expression in tumourigenesis: evidence for a significant link. PT Gomez del, SA Benitah, PF Valeron, C Espina, JC Lacal, Bioessays 2005 27 602 613 10.1002/bies.20238 15892119
107. Overexpression of RhoA is associated with poor prognosis in hepatocellular carcinoma. XR Li, F Ji, J Ouyang, W Wu, LY Qian, KY Yang, Eur J Surg Oncol 2006 32 1130 1134 10.1016/j.ejso.2006.05.012 16806792
108. Motility-related proteins as markers for head and neck squamous cell cancer. MT Abraham, MA Kuriakose, PG Sacks, H Yee, L Chiriboga, EL Bearer, MD Delacure, Laryngoscope 2001 111 1285 1289 10.1097/00005537-200107000-00027 11568556
109. Rho GTPases are over-expressed in human tumors. G Fritz, I Just, B Kaina, Int J Cancer 1999 81 682 687 10.1002/(SICI)1097-0215(19990531)81:5<682::AID- IJC2>3.0.CO;2-B 10328216
110. Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. A Horiuchi, T Imai, C Wang, S Ohira, Y Feng, T Nikaido, I Konishi, Lab Invest 2003 83 861 870 12808121
111. Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. T Kamai, T Tsujii, K Arai, K Takagi, H Asami, Y Ito, H Oshima, Clin Cancer Res 2003 9 2632 2641 12855641
112. Expression of seven main Rho family members in gastric carcinoma. Y Pan, F Bi, N Liu, Y Xue, X Yao, Y Zheng, D Fan, Biochem Biophys Res Commun 2004 315 686 691 10.1016/j.bbrc.2004.01.108 14975755
113. Clinical and prognostic significance of RhoA and RhoC gene expression in esophageal squamous cell carcinoma. A Faried, LS Faried, N Usman, H Kato, H Kuwano, Ann Surg Oncol 2007 14 3593 3601 10.1245/s10434-007-9562-x 17896152
114. Overexpression of RhoA, Rac1, and Cdc42 GTPases is associated with progression in testicular cancer. T Kamai, T Yamanishi, H Shirataki, K Takagi, H Asami, Y Ito, K Yoshida, Clin Cancer Res 2004 10 4799 4805 10.1158/1078-0432. CCR-0436-03 15269155
115. Rho GTPases: biochemistry and biology. AB Jaffe, A Hall, Annu Rev Cell Dev Biol 2005 21 247 269 10.1146/annurev.cellbio.21.020604.150721 16212495
116. The challenges of abundance: epithelial junctions and small GTPase signalling. VM Braga, AS Yap, Curr Opin Cell Biol 2005 17 466 474 10.1016/j.ceb.2005.08.012 16112561
117. Epithelium-mesenchyme: a balancing act of RhoGAP and RhoGEF. M Labouesse, Curr Biol 2004 14 508 R510 10.1016/j.cub.2004.06.039 15242630
118. Fibroblast-led collective invasion of carcinoma cells with differing roles for RhoGTPases in leading and following cells. C Gaggioli, S Hooper, C Hidalgo-Carcedo, R Grosse, JF Marshall, K Harrington, E Sahai, Nat Cell Biol 2007 9 1392 1400 10.1038/ncb1658 18037882
119. Genomic analysis of metastasis reveals an essential role for RhoC. EA Clark, TR Golub, ES Lander, RO Hynes, Nature 2000 406 532 535 10.1038/35020106 10952316
120. RhoC GTPase expression as a potential marker of lymph node metastasis in squamous cell carcinomas of the head and neck. CG Kleer, TN Teknos, M Islam, B Marcus, JS Lee, Q Pan, SD Merajver, Clin Cancer Res 2006 12 4485 4490 10.1158/1078-0432.CCR-06-0376 16899593
121. A novel putative low-affinity insulin-like growth factor-binding protein, LIBC (lost in inflammatory breast cancer), and RhoC GTPase correlate with the inflammatory breast cancer phenotype. KL van Golen, S Davies, ZF Wu, Y Wang, CD Bucana, H Root, S Chandrasekharappa, M Strawderman, SP Ethier, SD Merajver, Clin Cancer Res 1999 5 2511 2519 10499627
122. Differential molecular profiling between skin carcinomas reveals four newly reported genes potentially implicated in squamous cell carcinoma development. C Marionnet, C Lalou, K Mollier, M Chazal, G Delestaing, D Compan, O Verola, C Vilmer, J Cuminet, L Dubertret, N Basset-Seguin, Oncogene 2003 22 3500 3505 10.1038/sj.onc.1206571 12776202
123. Overexpression of the rhoC gene correlates with progression of ductal adenocarcinoma of the pancreas. H Suwa, G Ohshio, T Imamura, G Watanabe, S Arii, M Imamura, S Narumiya, H Hiai, M Fukumoto, Br J Cancer 1998 77 147 152 9459160
124. Genomic analysis reveals RhoC as a potential marker in hepatocellular carcinoma with poor prognosis. W Wang, LY Yang, GW Huang, WQ Lu, ZL Yang, JQ Yang, HL Liu, Br J Cancer 2004 90 2349 2355 15150600
125. Expression of RHOC is associated with metastasis of gastric carcinomas. T Kondo, K Sentani, N Oue, K Yoshida, H Nakayama, W Yasui, Pathobiology 2004 71 19 25 10.1159/000072958 14555841
126. RhoC promotes metastasis via activation of the Pyk2 pathway in prostate cancer. M Iiizumi, S Bandyopadhyay, SK Pai, M Watabe, S Hirota, S Hosobe, T Tsukada, K Miura, K Saito, E Furuta, W Liu, F Xing, H Okuda, A Kobaiashi, K Watabe, Cancer Res 2008 68 7613 7620 10.1158/0008-5472.CAN-07-6700 18794150
127. Higher expression of RhoC is related to invasiveness in non-small cell lung carcinoma. Y Shikada, I Yoshino, T Okamoto, S Fukuyama, T Kameyama, Y Maehara, Clin Cancer Res 2003 9 5282 5286 14614010
128. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. L Ma, J Teruya-Feldstein, RA Weinberg, Nature 2007 449 682 688 10.1038/nature06174 17898713
129. Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma. DI Bellovin, KJ Simpson, T Danilov, E Maynard, DL Rimm, P Oettgen, AM Mercurio, Oncogene 2006 25 6959 6967 10.1038/sj.onc.1209682 16715134
130. Stepping out of the flow: capillary extravasation in cancer metastasis. FL Miles, FL Pruitt, KL van Golen, CR Cooper, Clin Exp Metastasis 2008 25 305 324 10.1007/s10585-007-9098-2 17906932
131. RhoB in cancer suppression. M Huang, GC Prendergast, Histol Histopathol 2006 21 213 218 16329046
132. 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. AX Liu, N Rane, JP Liu, GC Prendergast, Mol Cell Biol 2001 21 6906 6912 10.1128/MCB.21.20.6906-6912.2001 11564874
133. Regulation of glioblastoma cell invasion by PKC iota and RhoB. RM Baldwin, DA Parolin, IA Lorimer, Oncogene 2008 27 3587 3595 10.1038/sj.onc. 1211027 18212741
134. Akt mediates Ras downregulation of RhoB, a suppressor of transformation, invasion, and metastasis. K Jiang, J Sun, J Cheng, JY Djeu, S Wei, S Sebti, Mol Cell Biol 2004 24 5565 5576 10.1128/MCB.24.12.5565-5576.2004 15169915
135. Src kinase modulates the activation, transport and signalling dynamics of fibroblast growth factor receptors. E Sandilands, S Akbarzadeh, A Vecchione, DG McEwan, MC Frame, JK Heath, EMBO Rep 2007 8 1162 1169 10.1038/sj.embor.7401097 17975556
136. Rac1 in human breast cancer: overexpression, mutation analysis, and characterization of a new isoform, Rac1b. A Schnelzer, D Prechtel, U Knaus, K Dehne, M Gerhard, H Graeff, N Harbeck, M Schmitt, E Lengyel, Oncogene 2000 19 3013 3020 10.1038/sj.onc.1203621 10871853
137. Overexpression of Rac-1 small GTPase binding protein in oral squamous cell carcinoma. SY Liu, CY Yen, SC Yang, WF Chiang, KW Chang, J Oral Maxillofac Surg 2004 62 702 707 10.1016/j.joms.2004.02.002 15170282
138. Rac1 is required for the formation of three germ layers during gastrulation. K Sugihara, N Nakatsuji, K Nakamura, K Nakao, R Hashimoto, H Otani, H Sakagami, H Kondo, S Nozawa, A Aiba, M Katsuki, Oncogene 1998 17 3427 3433 10.1038/sj.onc.1202595 10030666
139. Critical roles for Rac1 and Rac2 GTPases in B cell development and signaling. MJ Walmsley, SK Ooi, LF Reynolds, SH Smith, S Ruf, A Mathiot, L Vanes, DA Williams, MP Cancro, VL Tybulewicz, Science 2003 302 459 462 10.1126/science.1089709 14564011
140. Requirement for Rac1 in a K-ras induced lung cancer in the mouse. JL Kissil, MJ Walmsley, L Hanlon, KM Haigis, CF Bender Kim, A Sweet-Cordero, MS Eckman, DA Tuveson, AJ Capobianco, VL Tybulewicz, T Jacks, Cancer Res 2007 67 8089 8094 10.1158/0008-5472.CAN-07-2300 17804720
141. Mice deficient in the Rac activator Tiam1 are resistant to Ras-induced skin tumours. A Malliri, RA van der Kammen, K Clark, V van d, F Michiels, JG Collard, Nature 2002 417 867 871 10.1038/nature00848 12075356
142. Matrix-dependent Tiam1/Rac signaling in epithelial cells promotes either cell-cell adhesion or cell migration and is regulated by phosphatidylinositol 3-kinase. EE Sander, DS van, JP ten Klooster, T Reid, RA van der Kammen, F Michiels, JG Collard, J Cell Biol 1998 143 1385 1398 10.1083/jcb.143.5.1385 9832565
143. Tumor progression: Small GTPases and loss of cell-cell adhesion. E Lozano, M Betson, VM Braga, Bioessays 2003 25 452 463 10.1002/bies.10262 12717816
144. Deficiency of the hematopoietic cell-specific Rho family GTPase Rac2 is characterized by abnormalities in neutrophil function and host defense. AW Roberts, C Kim, L Zhen, JB Lowe, R Kapur, B Petryniak, A Spaetti, JD Pollock, JB Borneo, GB Bradford, SJ Atkinson, MC Dinauer, DA Williams, Immunity 1999 10 183 196 10.1016/S1074-7613(00)80019-9 10072071
145. Rac1 and Rac2 regulate macrophage morphology but are not essential for migration. AP Wheeler, CM Wells, SD Smith, FM Vega, RB Henderson, VL Tybulewicz, AJ Ridley, J Cell Sci 2006 119 2749 2757 10.1242/jcs.03024 16772332
146. Generation of rac3 null mutant mice: role of Rac3 in Bcr/Abl-caused lymphoblastic leukemia. YJ Cho, B Zhang, V Kaartinen, L Haataja, C de, J Groffen, N Heisterkamp, Mol Cell Biol 2005 25 5777 5785 10.1128/MCB.25.13.5777- 5785.2005 15964830
147. Roles of the Rac1 and Rac3 GTPases in human tumor cell invasion. AY Chan, SJ Coniglio, YY Chuang, D Michaelson, UG Knaus, MR Philips, M Symons, Oncogene 2005 24 7821 7829 10.1038/sj.onc.1208909 16027728
148. Cloning of a novel human Rac1b splice variant with increased expression in colorectal tumors. P Jordan, R Brazao, MG Boavida, C Gespach, E Chastre, Oncogene 1999 18 6835 6839 10.1038/sj.onc.1203233 10597294
149. Activated Rac1, but not the tumorigenic variant Rac1b, is ubiquitinated on Lys 147 through a JNK-regulated process. O Visvikis, P Lores, L Boyer, P Chardin, E Lemichez, G Gacon, FEBS J 2008 275 386 396 10.1111/j.1742-4658.2007. 06209.x 18093184
150. Structure-function based design of small molecule inhibitors targeting Rho family GTPases. N Nassar, J Cancelas, J Zheng, DA Williams, Y Zheng, Curr Top Med Chem 2006 6 1109 1116 10.2174/156802606777812095 16842149
151. Loss of RhoB expression in human lung cancer progression. J Mazieres, T Antonia, G Daste, C Muro-Cacho, D Berchery, V Tillement, A Pradines, S Sebti, G Favre, Clin Cancer Res 2004 10 2742 2750 10.1158/1078-0432.CCR-03-0149 15102679
152. Nonrandom 4p13 rearrangements of the RhoH/TTF gene, encoding a GTP-binding protein, in non-Hodgkin's lymphoma and multiple myeloma. C Preudhomme, C Roumier, MP Hildebrand, E Dallery-Prudhomme, D Lantoine, JL Lai, A Daudignon, C Adenis, F Bauters, P Fenaux, JP Kerckart, S Galiegue-Zouitina, Oncogene 2000 19 2023 2032 10.1038/sj.onc.1203521 10803463