Disease relevance of RHOC

• Expression of RHOC is associated with metastasis of gastric carcinomas [1].
• It has recently been reported that RHOC contributes to the metastatic phenotype of melanoma cells [1].
• In human mammary epithelial-RhoC breast cancer cells, p190-RhoC-C, but not p190-RhoA-C or p190-RhoB-C, reversed the anchorage-independent growth and invasion phenotypes caused by RhoC overexpression [2].
• Up-regulation of small GTPases, RhoA and RhoC, is associated with tumor progression in ovarian carcinoma [3].
• We developed a specific anti-RhoC antibody and studied archival breast tissues that comprise a broad spectrum of breast disease [4].
• Our results show a critical role of RhoC in metastasis of HCC, implicating RhoC as a potential therapeutic target to block HCC metastasis [5].

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

• In the highly metastatic A375-M human melanoma cells, p190-RhoC-C specifically reversed migration, and invasion phenotypes attributed to RhoC up-regulation [2].
• These results suggest that geranylgeranylation step of RhoA and RhoC could be a good therapeutic target for the prevention of invasion and metastasis of breast cancer cells [13].
• Reassignment of the human ARH9 RAS-related gene to chromosome 1p13-p21 [14].
• The human ARH9 gene (originally rhoC), a member of the RAS gene superfamily, was initially isolated on the basis of cross-hybridization with a RAS-related cDNA from the marine snail Aplysia [14].
• Fluorescence in situ hybridization to metaphase chromosomes with a genomic ARH9 clone refined the gene's localization to chromosome 1, bands p13-p21 [14].

Anatomical context of RHOC

• RHOC mRNA expression was confirmed in the gastric carcinoma cell lines [1].
• RHOC expression levels in primary tumor and their metastatic tumors were significantly higher than their corresponding nonneoplastic mucosa (p = 0.0357, and 0.0173, respectively; Wilcoxon signed rank test) [1].
• OBJECTIVES: RHOC, a member of the RAS-related small GTPase protein family, regulates cytoskeletal structures and has the potential to transform cultured cells [1].
• The ARH9 gene locus was previously assigned to the telomeric region of chromosome 5q by isotopic chromosomal in situ hybridization and Southern analysis of somatic cell hybrid DNAs; the gene was noted to cosegregate with the CSF1 gene locus in human-rodent somatic cell hybrids carrying partial chromosomes 5, together with other human chromosomes [14].
• RESULTS: RhoA, RhoC, and ROCK were more abundant in tumors and metastatic lymph nodes than in nontumor bladder and uninvolved lymph nodes (P < 0.0001) [15].

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

• In addition, analysis of matched pairs of primary and disseminated lesions demonstrated that expression of both RhoA and RhoC mRNA was significantly higher in metastatic than in primary tumors [3].
• Mitogen activated protein kinase pathway is involved in RhoC GTPase induced motility, invasion and angiogenesis in inflammatory breast cancer [21].
• Expression and significance of RhoC gene in hepatocellular carcinoma [22].
• We confirm the overexpression of E-Cadherin and RhoC GTPase in IBC [23].
• No interaction is found with RhoA, RhoC, or Rac1 proteins [24].

Analytical, diagnostic and therapeutic context of RHOC

• METHODS: We examined the expression of RHOC by quantitative RT-PCR in 51 cases of gastric carcinoma tissues from prior surgical cases (intestinal type: 24 cases, diffuse type: 27 cases) and in 8 gastric carcinoma cell lines [1].
• RhoC protein expression was confirmed by immunohistochemistry and Western blot analysis in several cases [25].
• By multivariate analysis, only RhoC was independently influenced in disease-free survival (P < 0.05), and RhoA and RhoC in overall survival (P < 0.001) [15].
• Protein levels of RhoA and RhoC in ESCC cell lines were visualised by Western blotting, and showed highest expression in TE-2 cells [26].
• Comparative microarray analysis of these clones further revealed that RhoC overexpression upregulated 108 genes whereas seven genes were down-regulated [27].

References