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Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells

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 mechan...

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Autores principales: Zhao, Junzhang, Zhou, Rui, Hui, Kaiyuan, Yang, Yang, Zhang, QiuYue, Ci, Yali, Shi, Lei, Xu, Caimin, Huang, Fang, Hu, Yu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Impact Journals LLC 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386651/
https://www.ncbi.nlm.nih.gov/pubmed/27902968
http://dx.doi.org/10.18632/oncotarget.13600
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author Zhao, Junzhang
Zhou, Rui
Hui, Kaiyuan
Yang, Yang
Zhang, QiuYue
Ci, Yali
Shi, Lei
Xu, Caimin
Huang, Fang
Hu, Yu
author_facet Zhao, Junzhang
Zhou, Rui
Hui, Kaiyuan
Yang, Yang
Zhang, QiuYue
Ci, Yali
Shi, Lei
Xu, Caimin
Huang, Fang
Hu, Yu
author_sort Zhao, Junzhang
collection PubMed
description 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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spelling pubmed-53866512017-04-26 Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells Zhao, Junzhang Zhou, Rui Hui, Kaiyuan Yang, Yang Zhang, QiuYue Ci, Yali Shi, Lei Xu, Caimin Huang, Fang Hu, Yu Oncotarget Research Paper 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. Impact Journals LLC 2016-11-25 /pmc/articles/PMC5386651/ /pubmed/27902968 http://dx.doi.org/10.18632/oncotarget.13600 Text en Copyright: © 2017 Zhao et al. http://creativecommons.org/licenses/by/3.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Paper
Zhao, Junzhang
Zhou, Rui
Hui, Kaiyuan
Yang, Yang
Zhang, QiuYue
Ci, Yali
Shi, Lei
Xu, Caimin
Huang, Fang
Hu, Yu
Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells
title Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells
title_full Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells
title_fullStr Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells
title_full_unstemmed Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells
title_short Selenite inhibits glutamine metabolism and induces apoptosis by regulating GLS1 protein degradation via APC/C-CDH1 pathway in colorectal cancer cells
title_sort selenite inhibits glutamine metabolism and induces apoptosis by regulating gls1 protein degradation via apc/c-cdh1 pathway in colorectal cancer cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5386651/
https://www.ncbi.nlm.nih.gov/pubmed/27902968
http://dx.doi.org/10.18632/oncotarget.13600
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