Lewis y antigen promotes p27 degradation by regulating ubiquitin-proteasome activity
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Mingbo Cai1,2,*, Shan Jin1,*, Lu Deng1, Liancheng Zhu1, Zhenhua Hu1,2, Dawo Liu1, Juanjuan Liu1, Mingzi Tan1, Jian Gao1, Huimin Wang1 and Bei Lin1
1Department of Obstetrics and Gynecology, Shengjing Hospital Affiliated to China Medical University, Heping District, Shenyang 110004, Liaoning, China
2Department of Obstetrics and Gynecology, The First Affiliated Hospital of Zhengzhou University, Zhongyuan District, Zhengzhou 450000, Henan, China
Keywords: Lewis y antigen, ovarian cancer, p27, autophagy, ubiquitin-proteasome pathway
Received: June 28, 2015 Accepted: October 02, 2017 Published: November 08, 2017
As a tumor-associated carbohydrate antigen, elevated expression of Lewis y promotes the malignant behaviors of tumor cells. Although our preliminary study showed that the increased expression of Lewis y antigen decreased the expression of cell cycle inhibitor protein p27, the relevant mechanism remains unclear. Autophagy and the ubiquitin-proteasome system are two main ways of intracellular protein degradation, whose abnormal activities are closely associated with progression of malignant tumors. In our present study, we constructed two stable transfected cell lines with high expression of Lewis y antigen, named CAOV3-FUT1 and SKOV3-FUT1. We showed that the proportion of cells at S phase was significantly increased after FUT1 transfection, whereas p27 protein was obviously decreased. The autophagy activity, the levels of ubiquitination, and chymotrypsin-like protease activity were increased remarkably in the transfected cells. Interestingly, Lewis y antigen promoted the degradation of p27 by increasing ubiquitin-proteasome activity. In the vivo studies, Lewis y antigen improved the tumorigenic ability of ovarian cancer cells in nude mice and reduced the expression of p27. These findings suggested that Lewis y antigen activated both the autophagy and ubiquitin-proteasome activity and promoted the degradation of p27 through the ubiquitin-proteasome pathway.
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