The effect of StarD13 on colorectal cancer proliferation and invasion. (c2013)

Abstract

Colon cancer is the cancer of the epithelial cells lining the colon. It is mainly divided into different stages according to invasiveness and metastatic ability of the tumor. Many mutations are acquired, leading to this malignancy. These occur in entities that greatly affect the cell cycle, cell signaling pathways, and cell movement, which all involve the action of Rho GTPases. The protein of our interest is DLC2, also known as StarD13 or START-GAP2, a GAP for Rho and Cdc42. Literature states that this protein is considered a tumor-suppressor in hepatocellular carcinoma. Previous work in our lab proved StarD13 to be a tumor suppressor in astrocytoma and in breast cancer. In this work, we studied the role of StarD13 in colon cancer. When overexpressed, StarD13 led to a decrease in cell proliferation in colon cancer cells. Consistently, knocking down StarD13 led to an increase in cell proliferation. This showed that, similarly to its role in astrocytoma and breast cancer, StarD13 seems to be a tumor suppressor in colon cancer as well. We were also interested in examining the role of StarD13 in cell motility. StarD13 knock down resulted in an inhibition of 2D cell motility. This is due to the inhibition of Rho, thus Rac dependant focal complexes are not formed nor detached for the cells to move forward. However, StarD13 knock down led to an increase in 3D cell motility. Although StarD13 was indeed a tumor suppressor in our colon cancer cells, as seen by its effect on cell proliferation, it was needed for cancer cell invasion. Our study further describes the role of StarD13 as a tumor suppressor as well as a RhoGAP.