Twist2 promotes kidney cancer cell proliferation and invasion by regulating ITGA6 and CD44 expression in the ECM-receptor interaction pathway

Hao-jie Zhang,1,2 Jing Tao,1 Lu Sheng,1 Xin Hu,3 Rui-ming Rong,2 Ming Xu,2 Tong-yu Zhu2 1Department of Urology, Huadong Hospital, Fudan University, Shanghai, People’s Republic of China; 2Department of Urology, Zhongshan Hospital, Fudan University, Shanghai, People’s Republic of China; 3Department of Breast Surgery, Key Laboratory of Breast Cancer in Shanghai, Fudan University Shanghai Cancer Center, Shanghai, People’sRepublic of China Abstract: Twist2 is a member of the basic helix-loop-helix (bHLH) family and plays a critical role in tumorigenesis. Growing evidence has proven that Twist2 is involved in tumor progression; however, the role of Twist2 in human kidney cancer and its underlying mechanisms remain unclear. Real-time polymerase chain reaction and Western blot analysis were used to detect the expression of Twist2 in kidney cancer cells and tissues. Cell proliferation, cell cycle, apoptosis, migration, and invasion assay were analyzed using the Cell Count Kit-8, flow cytometry, wound healing, and Transwell analysis, respectively. In this study, we showed that Twist2 was upregulated in human kidney cancer tissues compared with normal kidney tissues. Twist2 promoted cell proliferation, inhibited cell apoptosis, and augmented cell migration and invasion in human kidney-cancer-derived cells in vitro. Twist2 also promoted tumor growth invivo. Moreover, we found that the knockdown of Twist2 decreased the levels of ITGA6 and CD44 expression. This result indicates that Twist2 may promote migration and invasion of kidney cancer cells by regulating ITGA6 and CD44 expression. Therefore, our data demonstrated that Twist2 is involved in kidney cancer progression. The identification of the role of Twist2 in the migration and invasion of kidney cancer provides a potential appropriate treatment for human kidney cancer. Keywords: kidney cancer, Twist2, ITGA6, CD44