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

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.