SNAI1 overexpression induces stemness and promotes ovarian cancer cell invasion and metastasis

Abstract

Abstract. Ovarian cancer is the fifth most common cancer among women worldwide. Detection of metastasis of ovarian cancer is crucial for diagnosis and prolongs the life of patients. This study focused on whether SNAI1 overexpression relates to invasion of ovarian cancer in vitro and in vivo. Invasion, colony formation and wound healing assays and flow cytometric analysis were performed to test the invasion and proliferation of SKOV3 ovarian cancer cells after transfection. The effect of SNAI1 on ovarian cancer in vivo was validated using a murine xenograft model. In vitro, SNAI1 upregulation led to an increased percent of CD133 + SKOV3 cells and promoted SKOV3 cell invasion and proliferation. In vivo, the SNAI1 overexpression group showed the highest rate of tumor growth compared with SNAI2 and the control group (60 and 50%, respectively). Our results show that SNAI1 expression induces an increase in the number of CD133 + cells, a change important for the epithelial to mesenchymal transition and the proliferation in ovarian cancer. It is suggested that SNAI1 may serve as a novel target for ovarian cancer prediction and therapy. IntroductionOvarian cancer is the most lethal gynecological malignancy in the world, and is the fifth most common cancer diagnosis in females. At present, as there is no method of early detection, the majority of patients present with peritoneal dissemination and distant metastasis at the time of diagnosis (1-3). With disseminated disease, treatment is often unsuccessful and overall survival is short. The identification of an invasionrelated molecule associated with the early and rapid spread of ovarian cancer is the current focus of many investigators (4-6).Invasion and metastasis are biological hallmarks of malignancy (7). The molecular mechanism responsible for invasion and metastasis is a key area for investigation (8-10). A number of molecules related to tumor invasion and spread in ovarian cancer have been reported and include the following: Twist, E-cadherin and SNAI1. However, the molecular changes associated with acquisition of metastatic ability in ovarian cancer progression are poorly understood (11,12). The epithelial to mesenchymal transition (EMT) has been described as an important mechanism promoting invasion and causing metastasis of cancer. EMT describes a series of events during which epithelial cells lose many of their epithelial characteristics and take on properties typical of mesenchymal cells, which require complex changes in cell architecture and behavior (11,(13)(14)(15). The EMT is basically an embryonic trait through which cells adopt a phenotype more amenable to migration and invasion. Forced overexpression of SNAI1 in our present model demonstrated that SNAI1 incresed the percentage of CD133 + SKOV3 cells, an alteration important for the EMT and for cell proliferation. Our findings are the first evidence linking stemness to EMT and support a role of SNAI1 in metastasis. Materials and methodsCell culture and transfection. The ovarian cell line used in this stud...

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