The Role And Mechanism Of ANXA2 In Cholangiocarcinoma

Background:Annexin A2(ANXA2),a calcium-dependent phospholipid-binding protein,is reported to be associated with many human tumours.However,its role in the progression of cholangiocarcinoma(CCA)is still less known.In this study,we aimed to clarify the role of ANXA2 in CCA and to explore the mechanism involved.Methods:CCAs and adjacent non-cancerous bile duct specimens were collected from patients who underwent surgical resection.The expression of ANXA2 in CCA and cell lines were detected by real-time PCR,Immunohistochemistry and western blot.The effect and mechanism of ANXA2 in CCA were further investigated in vitro and in vivo functional studies.Results:The expression of ANXA2 was significantly higher in 50 CCA tissues than in adjacent non-cancerous bile duct tissues,and was correlated with poor overall survival(P=0.032).In vitro and in vivo functional studies showed that ANXA2 promoted CCA cell proliferation,migration and invasion.This may be due to ANXA2 facilitating the epithelial-mesenchymal transition(EMT).Moreover,the expression of?-catenin was up-regulated in human CCA tissues and positively correlated with ANXA2 expression.Activation and inhibition of Wnt/?-catenin signalling significantly affected the ANXA2 role in CCA.Conclusion:These data suggested that ANXA2 played an important role in growth and metastasis of CCA,via activating Wnt/?-catenin signalling.ANXA2 may be a potential therapeutic target for the treatment of CCA patients.