Distinctive role of starD 13 in serous ovarian carcinoma cell proliferation, metastasis, and invadopodia assembly. (c2019)

Abstract

Ovarian carcinoma is the second most leading cause of deaths among female reproductive system malignant tumors. Serous epithelial carcinomas have a poor treatment rates for it is most likely to be advanced when diagnosed due to its poor indications and symptoms. Ovarian serous carcinomas are mainly divided into different stages according to the invasiveness and metastatic ability of the tumor. Many mutations are acquired which lead to the development of this malignancy. This occur in entities that greatly affect the cell cycle, cell signaling pathways and cell motility, which all involve the action of Rho GTPases. The protein of interest in the present study was DLC2, also known as StarD13 or START-GAP2, a GTPaseactivating protein (GAP) for Rhoa and Cdc42. Literature data indicate that this protein is considered a tumor-suppressor in hepatocellular carcinoma. Previous research in our laboratory confirmed StarD13 as a tumor suppressor in astrocytoma, in breast cancer, and in colon cancer. In this study, we aim to investigate the role of StarD13 in cell migration, invasion, and proliferation. The results show that StarD13 is a tumor suppressor in ovarian serous carcinoma, it inhibits the function of cdc42 leading to the decrease in invadopodia assembly hence hindering invasion. StarD13 is needed for cell motility via its indirect effect on RhoA activation cycle. Moreover, StarD13 knockdown increased cell adhesiveness via the crosstalk between Cdc42 and Rac1 pathway. Therefore the cells were not being able to detach and move. Establishing the conclusion that StarD13 is in fact a tumor suppressor but it is needed for cell motility in ovarian cancer.