Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
Oncol Rep. 2014 Jan;31(1):505-15. doi: 10.3892/or.2013.2861. Epub 2013 Nov 20.
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.
结肠癌是一种发生于结肠上皮细胞的癌症。它主要根据肿瘤的侵袭性和转移性能力分为不同阶段。许多突变是获得性的，导致这种恶性肿瘤的发展。这些突变发生在极大地影响细胞周期、细胞信号通路和细胞迁移的实体中，所有这些都涉及到 Rho GTPases 的作用。本研究中感兴趣的蛋白质是 DLC2，也称为 StarD13 或 START-GAP2，是 Rho 和 Cdc42 的 GTPase 激活蛋白 (GAP)。文献数据表明，这种蛋白质被认为是肝细胞癌中的肿瘤抑制因子。我们实验室的先前研究证实 StarD13 是星形细胞瘤和乳腺癌中的肿瘤抑制因子。在本研究中，我们研究了 StarD13 在结肠癌中的作用。当过度表达时，StarD13 导致结肠癌细胞增殖减少。一致地，StarD13 的敲低导致细胞增殖增加。这表明，与星形细胞瘤和乳腺癌中的作用相似，StarD13 似乎也是结肠癌的肿瘤抑制因子。我们还研究了 StarD13 在细胞迁移中的作用。StarD13 的敲低导致 2D 细胞迁移受到抑制。这是由于 Rho 的抑制；因此，Rac 依赖性焦点复合物不能形成，细胞也不能向前移动。然而，StarD13 的敲低导致 3D 细胞迁移增加。尽管 StarD13 确实通过其对细胞增殖的影响成为我们结肠癌细胞中的肿瘤抑制因子，但它是癌细胞侵袭所必需的。本研究进一步描述了 StarD13 作为肿瘤抑制因子以及 Rho GAP 的作用。
