Encyclopedia of Signaling Molecules

2012 Edition
| Editors: Sangdun Choi


  • Nicolas Reymond
  • Francisco M. Vega
  • Anne J. Ridley
Reference work entry
DOI: https://doi.org/10.1007/978-1-4419-0461-4_59


Historical Background

RhoC was originally identified, together with its homologues RhoA and RhoB, as a Ras-related small GTPase (Madaule and Axel 1985). RhoA, RhoB, and RhoC together comprise the Rho subfamily of small GTPases characterized by their high homology within the Rho GTPase family. The human rhoc gene is on chromosome 1p13.1-p21. The rhoc gene is proposed to originate from a duplication of rhoa during evolution (Boureux et al. 2007). RhoA and RhoC are 93% identical at the protein level; the divergence is mainly concentrated in the so-called hypervariable region of the proteins at the C-terminus. Although multiple Rho subfamily GTPases exist in many eukaryotic organisms, specific RhoC orthologs do not exist outside vertebrates (Boureux et al. 2007). This together with the fact that, like RhoA, when RhoC is overexpressed in cells it induces the formation of actin stress fibers means that its specific functions were not...

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


  1. Arthur WT, Ellerbroek SM, et al. XPLN, a guanine nucleotide exchange factor for RhoA and RhoB, but not RhoC. J Biol Chem. 2002;277(45):42964–72.PubMedCrossRefGoogle Scholar
  2. Bellovin DI, Simpson KJ, et al. Reciprocal regulation of RhoA and RhoC characterizes the EMT and identifies RhoC as a prognostic marker of colon carcinoma. Oncogene. 2006;25(52):6959–67.PubMedCrossRefGoogle Scholar
  3. Bos JL, Rehmann H, et al. GEFs and GAPs: critical elements in the control of small G proteins. Cell. 2007;129(5):865–77.PubMedCrossRefGoogle Scholar
  4. Boureux A, Vignal E, et al. Evolution of the Rho family of ras-like GTPases in eukaryotes. Mol Biol Evol. 2007;24(1):203–16.PubMedCrossRefGoogle Scholar
  5. Bravo-Cordero JJ, Oser M, et al. A novel spatiotemporal RhoC activation pathway locally regulates cofilin activity at invadopodia. Curr Biol. 2011;21(8):635–44.PubMedCrossRefGoogle Scholar
  6. Chen Y, Yang Z, et al. Cullin mediates degradation of RhoA through evolutionarily conserved BTB adaptors to control actin cytoskeleton structure and cell movement. Mol Cell. 2009;35(6):841–55.PubMedCrossRefGoogle Scholar
  7. Clark EA, Golub TR, et al. Genomic analysis of metastasis reveals an essential role for RhoC. Nature. 2000;406(6795):532–5.PubMedCrossRefGoogle Scholar
  8. Dietrich KA, Schwarz R, et al. Specific induction of migration and invasion of pancreatic carcinoma cells by RhoC, which differs from RhoA in its localisation and activity. Biol Chem. 2009;390(10):1063–77.PubMedCrossRefGoogle Scholar
  9. Ellerbroek SM, Wennerberg K, et al. Serine phosphorylation negatively regulates RhoA in vivo. J Biol Chem. 2003;278(21):19023–31.PubMedCrossRefGoogle Scholar
  10. Faried A, Faried LS, et al. RhoA and RhoC proteins promote both cell proliferation and cell invasion of human oesophageal squamous cell carcinoma cell lines in vitro and in vivo. Eur J Cancer. 2006;42(10):1455–65.PubMedCrossRefGoogle Scholar
  11. Giampieri S, Manning C, et al. Localized and reversible TGFbeta signalling switches breast cancer cells from cohesive to single cell motility. Nat Cell Biol. 2009;11(11):1287–96.PubMedCrossRefGoogle Scholar
  12. Hakem A, Sanchez-Sweatman O, et al. RhoC is dispensable for embryogenesis and tumor initiation but essential for metastasis. Genes Dev. 2005;19(17):1974–9.PubMedCrossRefGoogle Scholar
  13. Iiizumi M, Bandyopadhyay S, et al. RhoC promotes metastasis via activation of the Pyk2 pathway in prostate cancer. Cancer Res. 2008;68(18):7613–20.PubMedCrossRefGoogle Scholar
  14. Jaffe AB, Hall A. Rho GTPases: biochemistry and biology. Annu Rev Cell Dev Biol. 2005;21:247–69.PubMedCrossRefGoogle Scholar
  15. Jiang L, Liu X, et al. Downregulation of the Rho GTPase signaling pathway is involved in the microRNA-138-mediated inhibition of cell migration and invasion in tongue squamous cell carcinoma. Int J Cancer. 2010;127(3):505–12.PubMedCrossRefGoogle Scholar
  16. Karlsson R, Pedersen ED, et al. Rho GTPase function in tumorigenesis. Biochim Biophys Acta. 2009;1796(2):91–8.PubMedGoogle Scholar
  17. Kitzing TM, Wang Y, et al. Formin-like 2 drives amoeboid invasive cell motility downstream of RhoC. Oncogene. 2010;29(16):2441–8.PubMedCrossRefGoogle Scholar
  18. Lochhead PA, Wickman G, et al. Activating ROCK1 somatic mutations in human cancer. Oncogene. 2010;29(17):2591–8.PubMedCrossRefGoogle Scholar
  19. Ma L, Teruya-Feldstein J, et al. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature. 2007;449(7163):682–8.PubMedCrossRefGoogle Scholar
  20. Madaule P, Axel R. A novel ras-related gene family. Cell. 1985;41(1):31–40.PubMedCrossRefGoogle Scholar
  21. Merajver SD, Usmani SZ. Multifaceted role of Rho proteins in angiogenesis. J Mammary Gland Biol Neoplasia. 2005;10(4):291–8.PubMedCrossRefGoogle Scholar
  22. Spangler B, Kappelmann M et al. ETS-1/RhoC signaling regulates the transcription factor c-Jun in melanoma. Int J Cancer. 2011Google Scholar
  23. Sun HW, Tong SL, et al. RhoA and RhoC -siRNA inhibit the proliferation and invasiveness activity of human gastric carcinoma by Rho/PI3K/Akt pathway. World J Gastroenterol. 2007;13(25):3517–22.PubMedGoogle Scholar
  24. Vega FM, Ridley AJ. Rho GTPases in cancer cell biology. FEBS Lett. 2008;582(14):2093–101.PubMedCrossRefGoogle Scholar
  25. Vega FM, Fruhwirth G, et al. RhoA and RhoC have distinct roles in migration and invasion by acting through different targets. J Cell Biol. 2011;193(4):655–65.PubMedCrossRefGoogle Scholar
  26. Wang W, Wu F, et al. RhoC is essential for angiogenesis induced by hepatocellular carcinoma cells via regulation of endothelial cell organization. Cancer Sci. 2008;99(10):2012–18.PubMedGoogle Scholar
  27. Wheeler AP, Ridley AJ. Why three Rho proteins? RhoA, RhoB, RhoC, and cell motility. Exp Cell Res. 2004;301(1):43–9.PubMedCrossRefGoogle Scholar
  28. Wu M, Wu ZF, et al. Characterization of the roles of RHOC and RHOA GTPases in invasion, motility, and matrix adhesion in inflammatory and aggressive breast cancers. Cancer. 2010;116(11 Suppl):2768–82.PubMedCrossRefGoogle Scholar
  29. Wu Y, Chen YC, et al. RhoC protein stimulates migration of gastric cancer cells through interaction with scaffold protein IQGAP1. Mol Med Rep. 2011;4(4):697–703.Google Scholar

Copyright information

© Springer Science+Business Media, LLC 2012

Authors and Affiliations

  • Nicolas Reymond
    • 1
  • Francisco M. Vega
    • 2
  • Anne J. Ridley
    • 1
  1. 1.Randall Division of Cell and Molecular BiophysicsKing’s College LondonLondonUK
  2. 2.Instituto de Biología Molecular y Celular del Cáncer, Centro de Investigación del Cáncer, Consejo Superior de Investigaciones Científicas (CSIC)-Universidad de SalamancaSalamancaSpain