Inhibition of Dishevelled-2 suppresses the biological behavior of pancreatic cancer by downregulating Wnt/β-catenin signaling.

Abstract

Dishevelled-2 (DVL2) has been proven to be involved in the tumorigenesis of several human cancers, such as colorectal cancer, lung cancer, prostate cancer, etc. However, its role in pancreatic ductal adenocarcinoma (PDAC) remains unclear. The present study investigated the effects of aberrantly expressed DVL2 on PDAC. A total of 97 pancreatic cancer (PC) samples and 85 adjacent normal samples were obtained from patients who were histopathologically diagnosed with primary PDAC. The present study demonstrated that DVL2 expression was upregulated in PDAC tissues and was positively associated with advanced clinical stage and lymph node metastasis in patients with PDAC. In addition, patients with high expression of DVL2 had a shorter overall survival rate compared with those with low expression. To elucidate the role of DVL2 in PDAC, lentivirus-mediated short hairpin RNA was used to silence DVL2 and its physiological function was analyzed in CFPAC-1 and PANC-1 cells. The results indicated that DVL2 downregulation significantly impaired its oncogenic functions including cell proliferation, migration, invasion and epithelial-mesenchymal transition. Furthermore, DVL2 knockdown inhibits the proliferation and invasion of PC cells in vivo. In addition, co-immunoprecipitation assays revealed that DVL2 interacted with β-catenin; knockdown of DVL2 reduced the expression level of β-catenin and inhibited β-catenin translocation into the nucleus. In conclusion the findings of the present study suggested that DVL2 may be a potential therapeutic target in the treatment of PDAC.