DLC2/StarD13 plays a role of a tumor suppressor in astrocytoma

Abstract

Astrocytomas are tumors occurring in young adult-hood. Astrocytic tumors can be classified into four grades according to histologic features: grades I, II, III and grade IV. Malignant tumors, those of grades III and IV, are characterized by uncontrolled proliferation, which is known to be regulated by the family of Rho GTPases. StarD13, a GAP for Rho GTPases, has been described as a tumor suppressor in hepatocellular carcinoma. In the present study, IHC analysis on grades I-IV brain tissues from patients showed StarD13 to be overexpressed in grades III and IV astrocytoma tumors when compared to grades I and II. However, when we mined the REMBRANDT data, we found that the mRNA levels of StarD13 are indeed higher in the higher grades but much lower than the normal tissues. Knocking down StarD13 using siRNA led to a decrease in cell death and an increase in cell viability, proving that StarD13 is indeed a tumor suppressor in astrocytomas. This was found to be mainly through cell cycle arrest independently of apoptosis. Finally, we detected an increase in p-ERK in StarD13 knockdown cells, uncovering a potential link between Rho GTPases and ERK activation.