Selenite Inhibits Glutamine Metabolism and Induces Apoptosis by Regulating GLS1 Protein Degradation Via APC/C-CDH1 Pathway in Colorectal Cancer Cells

Overview

Journal Oncotarget

Specialty Oncology

Date 2016 Dec 1

PMID 27902968

Citations 15

Authors

Junzhang Zhao

Rui Zhou

Kaiyuan Hui

Yang Yang

Qiuyue Zhang

Yali Ci

Lei Shi

Caimin Xu

Fang Huang

Yu Hu

Affiliations

Soon will be listed here.

Abstract

Glutaminolysis is important for metabolism and biosynthesis of cancer cells, and GLS is essential in the process. Selenite is widely regarded as a chemopreventive agent against cancer risk. Emerging evidence suggests that it also has chemotherapeutic potential in various cancer types, but the mechanism remains elusive. We demonstrate for the first time that supranutritional dose of selenite suppresses glutaminolysis by promoting GLS1 protein degradation and apoptosis. Mechanistically, selenite promotes association of APC/C-CDH1 with GLS1 and leads to GLS1 degradation by ubiquitination, this process is related to induction of PTEN expression. In addition, GLS1 expression is increased in human colorectal cancer tissues compared with normal mucosae. Our data provide a novel mechanistic explanation for the anti-cancer effect of selenite from a perspective of cell metabolism. Moreover, our results indicate that glutaminolysis especially GLS1 could be an attractive therapeutic target in colorectal cancer.

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