Overexpression of Ras Homologous C (RhoC) Induces Malignant Transformation of Hepatocytes In Vitro and in Nude Mouse Xenografts

Abstract

Ras homologous C (RhoC) is expressed in various cancers, including hepatocellular carcinoma (HCC). In this study, we first analyzed RhoC expression in 46 HCC tissue specimens and found that RhoC expression was significantly increased in HCC tissues compared to the adjacent normal liver tissues. Next, we investigated the role of RhoC in malignant transformation of normal hepatocytes. The HL7702 cell line was stably transfected with a RhoC expression vector and then subjected to cell proliferation, differentiation, colony formation, migration and invasion assays, as well as nude mouse xenograft assays. Gene expressions in these cells were determined using RT-PCR and Western blot. Overexpression of RhoC significantly promoted proliferation and anchorage-independent growth of HL7702 cells, but suppressed cell differentiation, as compared with the parental cells and the empty vector-transfected control cells. Moreover, RhoC overexpression induced migration and invasion of HL7702 cells in vitro. Molecularly, RhoC increased the expression of cell cycle-related genes, matrix metalloprotease 2 (MMP2), MMP9 and vascular endothelial growth factor (VEGF). In addition, RhoC-transfected cells formed tumors in nude mice, whereas vector-transfected HL7702 cells did not form any tumors in nude mice. This study demonstrated the role of RhoC overexpression in malignant transformation of normal human hepatocytes, suggesting that RhoC may function as an oncogene in hepatocytes.

The Role of RhoA, RhoB and RhoC GTPases in Cell Morphology, Proliferation and Migration in Human Cytomegalovirus (HCMV) Infected Glioblastoma Cells

“…The aforementioned observations prompted us to investigate moreover the average migration of non-infected and infected U373MG depleted one of the three Rho isoforms cells, with RhoB and RhoC knockdown cells having the faster healing rate and in accordance with studies highlighting the role of these GTPases mainly in malignant transformation and to a less extend in motility [75], whereas the movement of RhoA silenced cells is decreased (Fig. 6A and 6B), revealing once more the differential role of RhoA, RhoB and RhoC in migration and invasion [76][77][78].…”

Knockdown of RHOC by shRNA suppresses invasion and migration of cholangiocellular carcinoma cells via inhibition of MMP2, MMP3, MMP9 and epithelial-mesenchymal transition

“…To date, the molecular mechanisms by which RHOC promote tumor development and metastasis are not fully understood (26). Previous studies have demonstrated that RHOC promote cancer progression by regulating the expression of MMP genes (14,23,27). It is well established that MMPs induce cancer cell invasion and metastatic spread by degrading the extracellular matrix and other barriers (28).…”

Cytotoxic necrotizing factor 1 promotes bladder cancer angiogenesis through activating RhoC

“…RhoC was shown to induce angiogenesis by regulating endothelial cell migration and organization, 41 and to maintain vascular homeostasis by modulating the endothelial cell proliferation and permeability 42 . In addition, reports have shown that RhoC increases the VEGF expression 40,50‐52 . It was reported that p38 is involved in RhoC‐induced VEGF production in breast cancer cells 52 .…”