PLC gamma is required for RhoGDI2-mediated cisplatin resistance in gastric cancer

Abstract

Rho GDP dissociation inhibitor 2 (RhoGDI2) is a regulator of the Rho family GTPases. Recent work from our laboratory suggests that RhoGDI2 expression potentially enhances resistance to cisplatin as well as promotes tumor growth and malignant progression in gastric cancer. In this study, we demonstrate that phospholipase C-gamma (PLC gamma) is required for RhoGDI2-mediated cisplatin resistance and cancer cell invasion in gastric cancer. The levels of phosphorylated PLC gamma are markedly enhanced in RhoGDI2 -overexpressing SNU-484 cells and, by contrast, repressed in RhoGDI2-depleted MKN-28 cells. Depletion of PLC gamma expression or inhibition of its activity not only significantly increases cisplatin-induced apoptosis but also suppresses the invasive ability of RhoGDI2-overexpressing SNU-484 cells. Taken together, our results suggest that PLC gamma plays a key role in RhoGDI2-mediated cisplatin resistance and cell invasion in gastric cancer cells. (C) 2011 Elsevier Inc. All rights reserved.