Effect of StarD13 on colorectal cancer proliferation, motility and invasion

Nasrallah,Anita; Saykali,Bechara; Al Dimassi,Saleh; Khoury,Nathalie; Hanna,Samer; El-Sibai,Mirvat

doi:10.3892/or.2013.2861

Effect of StarD13 on colorectal cancer proliferation, motility and invasion

Authors:
- Anita Nasrallah
- Bechara Saykali
- Saleh Al Dimassi
- Nathalie Khoury
- Samer Hanna
- Mirvat El-Sibai
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Affiliations: Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, Lebanon
Published online on: November 20, 2013 https://doi.org/10.3892/or.2013.2861
Pages: 505-515

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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.

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