Specific role of RhoC in tumor invasion and metastasis

Abstract

Rho GTPases are regulators of many cellular functions and are often dysregulated in cancer. However, the precise role of Rho proteins for tumor development is not well understood. In breast cancer, overexpression of RhoC is linked with poor prognosis. Here, we aim to compare the function of RhoC and its homolog family member RhoA in breast cancer progression. We established stable breast epithelial cell lines with inducible expression of RhoA and RhoC, respectively. Moreover, we made use of Rho-activating bacterial toxins (Cytotoxic Necrotizing Factors) to stimulate the endogenous pool of Rho GTPases in benign breast epithelial cells and simultaneously knocked down specific Rho proteins. Whereas activation of Rho GTPases was sufficient to induce an invasive phenotype in three-dimensional culture systems, overexpression of RhoA or RhoC were not. However, RhoC but not RhoA was required for invasion, whereas RhoA and RhoC equally regulated proliferation. We further identified downstream target genes of RhoC involved in invasion and identified PTGS2 (COX-2) being preferentially upregulated by RhoC. Consistently, the COX-2 inhibitor Celecoxib blocked the invasive phenotype induced by the Rho-activating toxins.

Effects of RhoA and RhoC upon the sensitivity of prostate cancer cells to glutamine deprivation

“…RhoA or RhoC have been described to increase cell growth 18,20,21 . However, their stable overexpression may also lead to a decrease in cell growth caused by the profound changes in the cytoskeleton 22,23 , which is accordance with our results.…”

Cytotoxic necrotizing factor 1 promotes bladder cancer angiogenesis through activating RhoC

“…Previously, we reported that CNF1 increased prostate cancer cell migration and invasion to promote prostate cancer metastasis through activating Cdc42, 6 and CNF1 reduced macrophage phagocytosis to induce inflammation during acute UTIs partially through Cdc42 38 . Schmidt reported that CNF1 enhanced breast cancer cell invasion through activating RhoC 39 …”

Vaccination against RhoC induces long-lasting immune responses in patients with prostate cancer: results from a phase I/II clinical trial

“…For in vitro immunomonitoring, blood was taken before vaccination (visit 2), and after the 4th, 6th and 11th vaccinations (visits 6, 8 and 13). Follow-up samples were obtained every third month up to 13 months postvaccination (visits [14][15][16][17]. The study started in March 2017 and was completed in March 2019.…”