Phosphorylated LASS2 inhibits prostate carcinogenesis via negative regulation of Wnt/β‐catenin signaling. Issue 9 (14th April 2021)

• Record Type: Journal Article
• Authors: Zhang, Kuangen; Wu, Rui; Mei, Fang; Zhou, Yuhe; He, Lin; Liu, Yanhua; Zhao, Xuyang; You, Jiangfeng; Liu, Beiying; Meng, Qingyang; Pei, Fei
• Is Part Of: Journal of cellular biochemistry. Volume 122:Issue 9(2021)
• Page Start: 1048
• Page End: 1061
• Publication Date: 2021-04-14
• Subjects: LASS2 -- prostate cancer -- phosphorylation -- Wnt/β‐catenin -- ATP6V0C -- STK38 -- SCYL2; Cytochemistry -- Periodicals; 572
• DOI: 10.1002/jcb.29926
• Languages: English
• ISSNs: 0730-2312

Abstract

Abstract: LASS2 is a novel tumor‐suppressor gene and has been characterized as a ceramide synthase, which synthesizes very‐long acyl chain ceramides. However, LASS2 function and pathway‐related activity in prostate carcinogenesis are still largely unexplored. Here, we firstly report that LASS2 promotes β‐catenin degradation through physical interaction with STK38, SCYL2, and ATP6V0C via the ubiquitin–proteasome pathway, phosphorylation of LASS2 is essential for β‐catenin degradation, and serine residue 248 of LASS2 is illustrated to be a key phosphorylation site. Furthermore, we find that dephosphorylation of LASS2 at serine residue 248 significantly enhances prostate cancer cell growth and metastasis in vivo, indicating that phosphorylated LASS2 inhibits prostate carcinogenesis through negative regulation of Wnt/β‐catenin signaling. Thus, our findings implicate LASS2 as a potential biomarker and therapeutic target of prostate cancer.