Effect of StarD13 on colorectal cancer proliferation, motility and invasion

Abstract

Colon cancer is a cancer of the epithelial cells lining the colon. It is mainly divided into different stages according to the invasiveness and metastatic ability of the tumor. Many mutations are acquired which leads to the development of this malignancy. These 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 GTPase-activating protein (GAP) for Rho 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 and in breast cancer. In the present study, we investigated the role of StarD13 in colon cancer. When overexpressed, StarD13 was found to lead to a decrease in cell proliferation in colon cancer cells. Consistently, knockdown of StarD13 led to an increase in cell proliferation. This showed that, similarly to its role in astrocytoma and breast cancer, StarD13 appears to be a tumor suppressor in colon cancer as well. We also examined the role of StarD13 in cell motility. StarD13 knockdown resulted in the inhibition of 2D cell motility. This was due to the inhibition of Rho; consequently Rac-dependent focal complexes were not formed nor detached for the cells to move forward. However, StarD13 knockdown led to an increase in 3D cell motility. Although StarD13 was indeed a tumor suppressor in our colon cancer cells, as evidenced by its effect on cell proliferation, it was required for cancer cell invasion. The present study further describes the role of StarD13 as a tumor suppressor as well as a Rho GAP.

Differential regulation of rho GTPases during lung adenocarcinoma migration and invasion reveals a novel role of the tumor suppressor StarD13 in invadopodia regulation

“…Consistent with its role as a tumor suppressor, StarD13 also decreased cell motility in hepatocellular carcinoma [33], and localized to focal adhesions in HeLa cells [34]. We have confirmed the tumor suppressor function of StarD13 in a wide array of cancers including, breast cancer, colon cancer and astrocytoma [21][22][23][24]. Other groups have also reported low expression levels of StarD13 in in several tumor types, due to gene deletion or epigenetic modifications [15, 20-22, 24, 35-44].…”

“…Collectively, the results presented in Fig. 1 demonstrate that StarD13 acts as a tumor suppressor in lung cells and tissues, which has been indicated in other tumor types [15,21,22,24].…”

STARD13 is positively correlated with good prognosis and enhances 5-FU sensitivity via suppressing cancer stemness in hepatocellular carcinoma cells

“… 4 And it acts as a tumor suppressor in various cancers. 5 , 6 However, it is still unclear whether STARD13 holds critical roles in HCC cell stemness.…”

Knockdown of reticulon 4C by lentivirus inhibits human colorectal cancer cell growth

“…Colorectal cancer is a cancer of the cells lining the colorectal epithelium and has been identified as the third most common type of cancer worldwide (1,2). It is caused by a combination of a variety of factors, including diet, genetic mutations in several different loci, and reproductive or exogenous hormone use (3).…”