title: 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.
authors.affiliation: Department of Natural Sciences, Lebanese American University, Beirut 1102 2801, Lebanon.
authors.forename: Anita
authors.initials: A
authors.lastname: Nasrallah
authors.forename: Bechara
authors.initials: B
authors.lastname: Saykali
authors.forename: Saleh
authors.initials: S
authors.lastname: Al Dimassi
authors.forename: Nathalie
authors.initials: N
authors.lastname: Khoury
authors.forename: Samer
authors.initials: S
authors.lastname: Hanna
authors.forename: Mirvat
authors.initials: M
authors.lastname: El-Sibai
mesh_terms: D018938:Caco-2 Cells; D002448:Cell Adhesion / Q000235:genetics*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D049109:Cell Proliferation; D002470:Cell Survival / Q000235:genetics; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000473:pathology*; D020690:GTPase-Activating Proteins; D016147:Genes, Tumor Suppressor; D019073:HT29 Cells; D006801:Humans; D009361:Neoplasm Invasiveness; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis / Q000276:immunology; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics; D016211:Transforming Growth Factor alpha / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000096:biosynthesis / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000096:biosynthesis / Q000276:immunology; D020764:cdc42 GTP-Binding Protein / Q000235:genetics; D020830:rac1 GTP-Binding Protein / Q000235:genetics; D020742:rhoA GTP-Binding Protein / Q000235:genetics
chemical_list: C494826:BAX protein, human; D020690:GTPase-Activating Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D034741:RNA, Small Interfering; C473607:STARD13 protein, human; D016211:Transforming Growth Factor alpha; D053773:Transforming Growth Factor beta1; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D051028:bcl-2-Associated X Protein; D020764:cdc42 GTP-Binding Protein; D020830:rac1 GTP-Binding Protein; D020742:rhoA GTP-Binding Protein