Muscle-invasive or metastatic bladder cancer (BCa) is a life-threatening disease for patients, and tumor angiogenesis is believed to play a critical role in the progression of BCa. However, its underlying mechanism of tumor angiogenesis is still poorly understood. In this study, we discovered that RASAL2, a RAS GTPase activating protein, could inhibit BCa angiogenesis based on our shRNA/siRNA knockdown or ectopic cDNA expression experiments. Mechanistically, RASAL2 downregulation could enhance the phosphorylation of AKT and then subsequently upregulate the expression of ETS1 and VEGFA. Furthermore, there was a negative correlation between RASAL2 and VEGFA or CD31 expression in subcutaneous xenograft and human BCa specimens. Taken together, we provide a new insight into the molecular mechanism of BCa progression, in which RASAL2 can be a new therapeutic target.
Cellular signalling. 2018 Apr 24 [Epub ahead of print]
Ke Hui, Shiqi Wu, Yangyang Yue, Yanan Gu, Bing Guan, Xinyang Wang, Jer-Tsong Hsieh, Luke S Chang, Dalin He, Kaijie Wu
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China., Department of Urology, University of Texas Southwestern Medical Center, Dallas 75235, TX, USA., Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: ., Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an 710061, PR China. Electronic address: .