Data from Rho GTPase-Activating Protein Deleted in Liver Cancer Suppresses Cell Proliferation and Invasion in Hepatocellular Carcinoma

Abstract

<div>Abstract<p>Deleted in liver cancer (<i>DLC1</i>) is a candidate tumor suppressor gene recently isolated from human hepatocellular carcinoma. Structurally, DLC1 protein contains a conserved GTPase-activating protein for Rho family protein (RhoGAP) domain, which has been thought to regulate the activity of Rho family proteins. Previous studies indicated that <i>DLC1</i> was frequently inactivated in cancer cells. In the present study, we aimed to characterize the tumor suppressor roles of <i>DLC1</i> in hepatocellular carcinoma. We showed that <i>DLC1</i> significantly inhibited cell proliferation, anchorage-independent growth, and <i>in vivo</i> tumorigenicity when stably expressed in hepatocellular carcinoma cells. Moreover, <i>DLC1</i> expression greatly reduced the motility and invasiveness of hepatocellular carcinoma cells. With RhoGAP-deficient <i>DLC1</i> mutant (<i>DLC1-K714E</i>), we showed that the RhoGAP activity was essential for <i>DLC1</i>-mediated tumor suppressor function. Furthermore, the 292– to 648–amino acid region and the steroidogenic acute regulatory related lipid transfer domain played an auxiliary role to RhoGAP and tumor suppressor function of DLC1. Taken together, our findings showed that <i>DLC1</i> functions as a tumor suppressor in hepatocellular carcinoma and provide the first evidence to support the hypothesis that <i>DLC1</i> suppresses cancer cell growth by negatively regulating the activity of Rho proteins.</p></div>