Patients with prostate cancer (PCa) have a high incidence of relapse and metastasis. Unfortunately, the molecular mechanisms underlying these processes have not been fully elucidated. In our study, we demonstrate that MUC15, a member of the mucin family, is a novel tumor suppressor in PCa that modulates epithelial-mesenchymal transition (EMT) and cancer stemness, contributing to PCa metastasis. First, MUC15 expression was found to be decreased in PCa tissues compared with para-carcinoma tissues. Moreover, we observed thatMUC15suppressed cell migration and invasion, both in vitro and in vivo, but had no effect on cell proliferation. Mechanistically, knockdown of MUC15 increased GSK3β phosphorylation and promoted β-catenin nuclear translocation. Therefore, the β-catenin-specific inhibitors XAV939 and PRI-724 rescued EMT in MUC15-deficientcell lines. Taken together, these results indicate that MUC15 is downregulated in PCa tissues and serves as a potential target to prevent PCa metastasis, which can inhibit EMT and cancer stemness via the GSK3β/β-catenin signaling pathway.
Cellular signalling. 2021 Apr 21 [Epub ahead of print]
Shiqi Wu, Yangyang Yue, Yanan Gu, Qi Wang, Tianjie Liu, Lei Li, Xinyang Wang, Luke S Chang, Dalin He, Kaijie Wu
Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China., Department of Hepatobiliary Surgery, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China., Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China. Electronic address: ., Department of Urology, First Affiliated Hospital of Xi'an Jiaotong University, Xi'an, PR China. Electronic address: .