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Gene Review

RHOC  -  ras homolog family member C

Homo sapiens

Synonyms: ARH9, ARHC, H9, RHOH9, Rho cDNA clone 9, ...
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Disease relevance of RHOC


High impact information on RHOC

  • Targeted Disruption of Protein Kinase C{varepsilon} Reduces Cell Invasion and Motility through Inactivation of RhoA and RhoC GTPases in Head and Neck Squamous Cell Carcinoma [6].
  • We conclude that collagen I attachment mediated by alpha(2)beta(1) initiates motility programs through RhoC and suggest a mechanism for prostate cancer metastasis to the bone [7].
  • PKC epsilon-deficient clones were found to have lower RhoC GTPase protein levels and activation [8].
  • We have used a stable retroviral RNA interference approach to generate invasive breast carcinoma cells (SUM-159 cells) that lack either RhoA or RhoC expression [9].
  • Although they share over 85% sequence identity, RhoA, RhoB, and RhoC appear to play distinct roles in cell transformation and metastasis [2].

Chemical compound and disease context of RHOC

  • RhoC inhibition, either pharmacologically with C3 exotransferase or molecularly through expression of a dominant-negative RhoC, promotes IGF-I stimulated random motility but decreases in vitro invasion and experimental metastases [10].
  • Also the ratios exhibited different behaviors, for example the total adenine nucleotides total guanine nucleotides ratio (sigma A/sigma G) was enhanced in H9/HTLV-III cells with respect to H9 and unaltered in 8E51 with respect to A3.01 cells [11].
  • We have studied the purine nucleotide metabolism in the following cell lines: a), H9 (continuous human T-cell line) and H9/HTLV-III (H9 cell line, infected with RT+ HIV-I virus); b), A3.01 (human lymphoblastoid cell line CD4+) and 8E51 (line A3.01 permanently transfected with RT-HIV-I virus) [11].
  • WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer [12].

Biological context of RHOC


Anatomical context of RHOC


Associations of RHOC with chemical compounds

  • The inhibitory effects of fluvastatin, GGTI-298 and FTI-277 on MDA-MB-231 cell invasion were shown to correlate well with inhibition of the membrane localization of RhoA and RhoC, but not with Ras [13].
  • In accordance with these findings, Scambio does not activate either Rac or Cdc42 but rather, stimulates guanine nucleotide exchange on RhoA and its close relative, RhoC [16].
  • In the present study, we assessed the effect of the FTI L-744,832 on RhoC-overexpressing IBC and RhoC-transfected human mammary epithelial (HME-RhoC) cells [17].
  • 4. The depression of IGABA produced by SP was inhibited by H-7 and PKC(19-36), protein kinase C (PKC) inhibitors, but not by H-9 and HA-1004, protein kinase A inhibitors [18].
  • Human H9 cells proliferation is differently controlled by vasoactive intestinal peptide or peptide histidine methionine: implication of a GTP-insensitive form of VPAC1 receptor [19].

Regulatory relationships of RHOC

  • Recently, van Golen and Merajver and their colleagues have demonstrated that FTIs will recruit RhoB to suppress IBC cell phenotypes or neoplastic transformation of human mammary epithelial cells by RhoC, a key oncogenic driver in IBC [20].

Other interactions of RHOC


Analytical, diagnostic and therapeutic context of RHOC


  1. Expression of RHOC is associated with metastasis of gastric carcinomas. Kondo, T., Sentani, K., Oue, N., Yoshida, K., Nakayama, H., Yasui, W. Pathobiology (2004) [Pubmed]
  2. A novel strategy for specifically down-regulating individual Rho GTPase activity in tumor cells. Wang, L., Yang, L., Luo, Y., Zheng, Y. J. Biol. Chem. (2003) [Pubmed]
  3. Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma. Horiuchi, A., Imai, T., Wang, C., Ohira, S., Feng, Y., Nikaido, T., Konishi, I. Lab. Invest. (2003) [Pubmed]
  4. Characterization of RhoC expression in benign and malignant breast disease: a potential new marker for small breast carcinomas with metastatic ability. Kleer, C.G., van Golen, K.L., Zhang, Y., Wu, Z.F., Rubin, M.A., Merajver, S.D. Am. J. Pathol. (2002) [Pubmed]
  5. Inhibition of invasion and metastasis of hepatocellular carcinoma cells via targeting RhoC in vitro and in vivo. Wang, W., Wu, F., Fang, F., Tao, Y., Yang, L. Clin. Cancer Res. (2008) [Pubmed]
  6. Targeted Disruption of Protein Kinase C{varepsilon} Reduces Cell Invasion and Motility through Inactivation of RhoA and RhoC GTPases in Head and Neck Squamous Cell Carcinoma. Pan, Q., Bao, L.W., Teknos, T.N., Merajver, S.D. Cancer Res. (2006) [Pubmed]
  7. Type I Collagen Receptor ({alpha}2{beta}1) Signaling Promotes the Growth of Human Prostate Cancer Cells within the Bone. Hall, C.L., Dai, J., van Golen, K.L., Keller, E.T., Long, M.W. Cancer Res. (2006) [Pubmed]
  8. Protein kinase C epsilon is a predictive biomarker of aggressive breast cancer and a validated target for RNA interference anticancer therapy. Pan, Q., Bao, L.W., Kleer, C.G., Sabel, M.S., Griffith, K.A., Teknos, T.N., Merajver, S.D. Cancer Res. (2005) [Pubmed]
  9. Functional analysis of the contribution of RhoA and RhoC GTPases to invasive breast carcinoma. Simpson, K.J., Dugan, A.S., Mercurio, A.M. Cancer Res. (2004) [Pubmed]
  10. RhoC GTPase is required for PC-3 prostate cancer cell invasion but not motility. Yao, H., Dashner, E.J., van Golen, C.M., van Golen, K.L. Oncogene (2006) [Pubmed]
  11. Purine ribonucleotide content in infected HIV-RT+ and HIV-RT- lymphoblastoid cell lines. Carlucci, F., Tabucchi, A., Rosi, F., Pagani, R., Leoncini, R., Pizzichini, M., Marinello, E. Biomed. Pharmacother. (1996) [Pubmed]
  12. WISP3 and RhoC guanosine triphosphatase cooperate in the development of inflammatory breast cancer. Kleer, C.G., Zhang, Y., Pan, Q., Gallagher, G., Wu, M., Wu, Z.F., Merajver, S.D. Breast Cancer Res. (2004) [Pubmed]
  13. Inhibition of transendothelial migration and invasion of human breast cancer cells by preventing geranylgeranylation of Rho. Kusama, T., Mukai, M., Tatsuta, M., Nakamura, H., Inoue, M. Int. J. Oncol. (2006) [Pubmed]
  14. Reassignment of the human ARH9 RAS-related gene to chromosome 1p13-p21. Morris, S.W., Valentine, M.B., Kirstein, M.N., Huebner, K. Genomics (1993) [Pubmed]
  15. Significant association of Rho/ROCK pathway with invasion and metastasis of bladder cancer. Kamai, T., Tsujii, T., Arai, K., Takagi, K., Asami, H., Ito, Y., Oshima, H. Clin. Cancer Res. (2003) [Pubmed]
  16. Scambio, a novel guanine nucleotide exchange factor for Rho. Curtis, C., Hemmeryckx, B., Haataja, L., Senadheera, D., Groffen, J., Heisterkamp, N. Mol. Cancer (2004) [Pubmed]
  17. Reversion of RhoC GTPase-induced inflammatory breast cancer phenotype by treatment with a farnesyl transferase inhibitor. van Golen, K.L., Bao, L., DiVito, M.M., Wu, Z., Prendergast, G.C., Merajver, S.D. Mol. Cancer Ther. (2002) [Pubmed]
  18. Substance P suppresses GABAA receptor function via protein kinase C in primary sensory neurones of bullfrogs. Yamada, K., Akasu, T. J. Physiol. (Lond.) (1996) [Pubmed]
  19. Human H9 cells proliferation is differently controlled by vasoactive intestinal peptide or peptide histidine methionine: implication of a GTP-insensitive form of VPAC1 receptor. Goursaud, S., Pineau, N., Becq-Giraudon, L., Gressens, P., Muller, J.M., Janet, T. J. Neuroimmunol. (2005) [Pubmed]
  20. Farnesyltransferase inhibitors: potential therapeutic for inflammatory breast cancer? Prendergast, G.C. Breast disease. (2002) [Pubmed]
  21. Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer. van Golen, K.L., Bao, L.W., Pan, Q., Miller, F.R., Wu, Z.F., Merajver, S.D. Clin. Exp. Metastasis (2002) [Pubmed]
  22. Expression and significance of RhoC gene in hepatocellular carcinoma. Wang, W., Yang, L.Y., Yang, Z.L., Huang, G.W., Lu, W.Q. World J. Gastroenterol. (2003) [Pubmed]
  23. Validation of a tissue microarray to study differential protein expression in inflammatory and non-inflammatory breast cancer. Van den Eynden, G.G., Van der Auwera, I., Van Laere, S., Colpaert, C.G., van Dam, P., Merajver, S., Kleer, C.G., Harris, A.L., Van Marck, E.A., Dirix, L.Y., Vermeulen, P.B. Breast Cancer Res. Treat. (2004) [Pubmed]
  24. RhoGDI-3 is a new GDP dissociation inhibitor (GDI). Identification of a non-cytosolic GDI protein interacting with the small GTP-binding proteins RhoB and RhoG. Zalcman, G., Closson, V., Camonis, J., Honoré, N., Rousseau-Merck, M.F., Tavitian, A., Olofsson, B. J. Biol. Chem. (1996) [Pubmed]
  25. Higher expression of RhoC is related to invasiveness in non-small cell lung carcinoma. Shikada, Y., Yoshino, I., Okamoto, T., Fukuyama, S., Kameyama, T., Maehara, Y. Clin. Cancer Res. (2003) [Pubmed]
  26. RhoA and RhoC proteins promote both cell proliferation and cell invasion of human oesophageal squamous cell carcinoma cell lines in vitro and in vivo. Faried, A., Faried, L.S., Kimura, H., Nakajima, M., Sohda, M., Miyazaki, T., Kato, H., Usman, N., Kuwano, H. Eur. J. Cancer (2006) [Pubmed]
  27. RhoC induces differential expression of genes involved in invasion and metastasis in MCF10A breast cells. Wu, M., Wu, Z.F., Kumar-Sinha, C., Chinnaiyan, A., Merajver, S.D. Breast Cancer Res. Treat. (2004) [Pubmed]
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