TROP2 promotes proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT

// Xinxing Li 1, * , Shifeng Teng 1, * , Yanyan Zhang 1, * , Weigang Zhang 1 , Xianwen Zhang 1 , Kai Xu 1 , Houshan Yao 1 , Jun Yao 1 , Haolu Wang 2 , Xiaowen Liang 2 and Zhiqian Hu 1 1 Department of General Surgery, Changzheng Hospital, The Second Military Medical University, Shanghai 200003, China 2 Therapeutics Research Centre, School of Medicine, The University of Queensland, Princess Alexandra Hospital, Woolloongabba QLD 4102, Australia * These authors have contributed equally to this work Correspondence to: Xinxing Li, email: xingxin123456@sina.com Xiaowen Liang, email: x.liang@uq.edu.au Zhiqian Hu, email: huzhiq163@163.com Keywords: gallbladder cancer, TROP2, AKT, EMT Received: September 30, 2016     Accepted: March 21, 2017     Published: April 03, 2017 ABSTRACT The human trophoblast cell surface antigen 2 (TROP2) is overexpressed in many cancers. However, its effect on proliferation, migration and metastasis of gallbladder cancer remains unclear. In this study, we found that TROP2 was highly expressed in gallbladder cancer. Overexpression of TROP2 was associated with poor prognosis. Knockdown of TROP2 in gallbladder cancer cell lines strongly inhibited the cell proliferation, clone formation, invasion and migration in vitro , while TROP2 overexpression had opposite effects. In addition, knockdown of TROP2 increased the expression of total PTEN, p-PTEN and PDK-1 but reduced p-AKT via PI3K/AKT pathway. TROP2 downregulation also inhibited vimentin and increased E-cadherin expression during epithelial-mesenchymal transition (EMT). Moreover, gallbladder cancer cells with TROP2 knockdown formed smaller xenografted tumors in vivo . In consistent with in vitro results, TROP2 inhibition decreased Akt phosphorylation, increased PTEN expression and postponed EMT of gallbladder cancer cells in vivo . In conclusion, we revealed that TROP2 promoted the proliferation, migration and metastasis of gallbladder cancer cells by regulating PI3K/AKT pathway and inducing EMT. TROP2 could serve as a potential prognostic biomarker and therapeutic target for the clinical management of gallbladder cancer.