PIWIL2 stabilizes β-catenin to promote cell cycle and proliferation in tumor cells

• Published in: Biochemical and biophysical research communications Vol. 516; no. 3; pp. 819 - 824
• Main Authors: Qiu, Bojun, Zeng, Jiarong, Zhao, Xu, Huang, Lian, Ma, Tengjiao, Zhu, Yingchuan, Liu, Man, Tao, Dachang, Liu, Yunqiang, Lu, Yilu, Ma, Yongxin
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 27.08.2019
• Subjects: GSK3β; PIWIL2; β-Catenin; β-Catenin/CyclinD1 pathway; PIWIL2; GSK3β; β-Catenin; β-Catenin/CyclinD1 pathway
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2019.06.136

PIWIL2 belongs to the PIWI protein subfamily and is widely expressed in a variety of tumors. Previous studies have shown that PIWIL2 has the characteristics of oncogene. Recently we reported that PIWIL2 suppresses GSK3β activity to regulate circadian rhythms through SRC-PI3K-AKT pathway. As GSK3β is a key part of the β-catenin destruction complex, it plays a vital role in regulating the degradation of β-catenin. Besides, the activated β-catenin/CyclinD1 pathway is involved in the proliferation of tumor cells. It is intriguing to investigate whether PIWIL2 regulates β-catenin and downstream pathway. In this study, we found that PIWIL2 suppressed GSK3β induced phosphorylation and ubiquitination of β-catenin, and thus increased β-catenin accumulation in the nucleus. By up-regulating β-catenin and CyclinD1, PIWIL2 can promote cell cycle and proliferation in tumor cells. Taken together, our results revealed a novel function of PIWIL2 in regulating β-catenin/CyclinD1 pathway in tumor cells, providing a new perspective for PIWIL2 as an oncogene. •PIWIL2 suppresses the phosphorylation and ubiquitination degradation of β-catenin via GSK3β.•PIWIL2 promotes β-catenin nuclear accumulation.•PIWIL2 activates β-catenin/CyclinD1 pathway and thereby regulates the cell cycle and proliferation of tumor cells.