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.
Highlights
Gallbladder cancer (GBC) is the most common malignancy of biliary system with low curative resection rate (10–30%), low response rate to chemotherapy, and poor prognosis (5-year survival less than 5%) [1, 2, 3]
We suggest that trophoblast cell surface antigen 2 (TROP2) could serve as a potential prognostic biomarker and therapeutic target for the clinical management of GBC
Overexpression of TROP2 was associated with poor prognosis of GBC
Summary
Gallbladder cancer (GBC) is the most common malignancy of biliary system with low curative resection rate (10–30%), low response rate to chemotherapy, and poor prognosis (5-year survival less than 5%) [1, 2, 3]. There is urgent need to reveal detailed signal pathways involved in GBC proliferation, migration and metastasis, which may provide potential prognostic biomarkers and therapeutic targets for the clinical management of GBC. TROP2 overexpression has been reported to be associated with poor survival, tumor aggressiveness and metastasis [6]. It was involved in many signaling pathways of cell proliferation, survival and self-renewal [14]. Liu et al found that TROP2 promoted the proliferation and invasion of cervical cancer cells by regulating ERK www.impactjournals.com/oncotarget signaling pathway [9]. We revealed that TROP2 promoted the proliferation, migration and metastasis of GBC cells by regulating PI3K/AKT pathway and inducing epithelial-mesenchymal transition (EMT). We suggest that TROP2 could serve as a potential prognostic biomarker and therapeutic target for the clinical management of GBC
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