C3G is a guanine nucleotide exchange factor (GEF) for Rap1 and R-Ras, but it also acts through mechanisms independent of its GEF activity. C3G is essential for embryonic development based on its role in adhesion. Accordingly, it regulates functions related to cytoeskeletal remodelling such as migration and invasion. Its role in cancer is controversial, acting either as a tumour mediator or suppressor. Previously, we have found that C3G knock-down enhanced the migratory and invasive capacity of mouse embryonic fibroblasts and HCT116 colon carcinoma cells through hyperactivation of p38a. Based on this, we aimed to explore if C3G also regulates these processes in hepatocarcinoma (HCC) cells as well as in oval cells, bipotential hepatic progenitors that play an important role in liver regeneration after severe liver damage but have been also involved in HCC development. To do so, we have knocked-down C3G expression in several HCC cell lines displaying different degrees of epithelial phenotype and oval cell lines. Our results indicate that C3G knock-down increased migration and invasion of both HCC and oval cells. Based on the relevance of the epithelial-mesenchymal transition (EMT) for the acquisition of a more migratory and invasive cell phenotype, we are investigating the potential role of C3G on the regulation of EMT under basal conditions and upon induction by TGF-B. Our preliminary results indicate that C3G knock-down promotes E-cadherin loss and controls the expression of the EMT-inducing transcription factors Snail 1, Zeb 1/2 and Twist.

Resumen del trabajo presentado al XXXXVIII Congreso de la Sociedad Española de Bioquímica y Biología Molecular (SEBBM), celebrado en Valencia del 7 al 10 de septiembre de 2015.

Peer reviewed