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Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis

As a hallmark of cancer, the Warburg effect (aerobic glycolysis) confers a selective advantage for the survival and proliferation of cancer cells. Due to frequent aberration of upstream proto-oncogenes and tumor suppressors, hyperactive mammalian/mechanistic target of rapamycin (mTOR) is a potent in...

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Autores principales: Sun, Qian, Li, Shuzhan, Wang, Yanan, Peng, Haiyong, Zhang, Xiying, Zheng, Yu, Li, Chunjia, Li, Li, Chen, Rongrong, Chen, Xinxin, Bai, Wenjing, Jiang, Xiangli, Liu, Liang, Wei, Feng, Wang, Boshi, Zhang, Yu, Li, Hui, Ren, Xiubao, Zhang, Hongbing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988759/
https://www.ncbi.nlm.nih.gov/pubmed/29362480
http://dx.doi.org/10.1038/s41418-017-0034-y
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author Sun, Qian
Li, Shuzhan
Wang, Yanan
Peng, Haiyong
Zhang, Xiying
Zheng, Yu
Li, Chunjia
Li, Li
Chen, Rongrong
Chen, Xinxin
Bai, Wenjing
Jiang, Xiangli
Liu, Liang
Wei, Feng
Wang, Boshi
Zhang, Yu
Li, Hui
Ren, Xiubao
Zhang, Hongbing
author_facet Sun, Qian
Li, Shuzhan
Wang, Yanan
Peng, Haiyong
Zhang, Xiying
Zheng, Yu
Li, Chunjia
Li, Li
Chen, Rongrong
Chen, Xinxin
Bai, Wenjing
Jiang, Xiangli
Liu, Liang
Wei, Feng
Wang, Boshi
Zhang, Yu
Li, Hui
Ren, Xiubao
Zhang, Hongbing
author_sort Sun, Qian
collection PubMed
description As a hallmark of cancer, the Warburg effect (aerobic glycolysis) confers a selective advantage for the survival and proliferation of cancer cells. Due to frequent aberration of upstream proto-oncogenes and tumor suppressors, hyperactive mammalian/mechanistic target of rapamycin (mTOR) is a potent inducer of the Warburg effect. Here, we report that overexpression of a glycolytic enzyme, phosphoglyceric acid mutase-1 (PGAM1), is critical to oncogenic mTOR-mediated Warburg effect. mTOR stimulated PGAM1 expression through hypoxia-inducible factor 1α-mediated transcriptional activation. Blockage of PGAM1 suppressed mTOR-dependent glycolysis, cell proliferation, and tumorigenesis. PGAM1 expression and mTOR activity were positively correlated in non-small cell lung cancer (NSCLC) tissues and PGAM1 abundance was an adverse predictor for patient survival. PGAM1 is thus a downstream effector of mTOR signaling pathway and mTOR-PGAM1 signaling cascade may contribute to the development of Warburg effect observed in cancer. We consider PGAM1 as a novel prognostic biomarker for NSCLC and a therapeutic target for cancer.
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spelling pubmed-59887592018-06-20 Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis Sun, Qian Li, Shuzhan Wang, Yanan Peng, Haiyong Zhang, Xiying Zheng, Yu Li, Chunjia Li, Li Chen, Rongrong Chen, Xinxin Bai, Wenjing Jiang, Xiangli Liu, Liang Wei, Feng Wang, Boshi Zhang, Yu Li, Hui Ren, Xiubao Zhang, Hongbing Cell Death Differ Article As a hallmark of cancer, the Warburg effect (aerobic glycolysis) confers a selective advantage for the survival and proliferation of cancer cells. Due to frequent aberration of upstream proto-oncogenes and tumor suppressors, hyperactive mammalian/mechanistic target of rapamycin (mTOR) is a potent inducer of the Warburg effect. Here, we report that overexpression of a glycolytic enzyme, phosphoglyceric acid mutase-1 (PGAM1), is critical to oncogenic mTOR-mediated Warburg effect. mTOR stimulated PGAM1 expression through hypoxia-inducible factor 1α-mediated transcriptional activation. Blockage of PGAM1 suppressed mTOR-dependent glycolysis, cell proliferation, and tumorigenesis. PGAM1 expression and mTOR activity were positively correlated in non-small cell lung cancer (NSCLC) tissues and PGAM1 abundance was an adverse predictor for patient survival. PGAM1 is thus a downstream effector of mTOR signaling pathway and mTOR-PGAM1 signaling cascade may contribute to the development of Warburg effect observed in cancer. We consider PGAM1 as a novel prognostic biomarker for NSCLC and a therapeutic target for cancer. Nature Publishing Group UK 2018-01-23 2018-06 /pmc/articles/PMC5988759/ /pubmed/29362480 http://dx.doi.org/10.1038/s41418-017-0034-y Text en © ADMC Associazione Differenziamento e Morte Cellulare 2018 Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/.
spellingShingle Article
Sun, Qian
Li, Shuzhan
Wang, Yanan
Peng, Haiyong
Zhang, Xiying
Zheng, Yu
Li, Chunjia
Li, Li
Chen, Rongrong
Chen, Xinxin
Bai, Wenjing
Jiang, Xiangli
Liu, Liang
Wei, Feng
Wang, Boshi
Zhang, Yu
Li, Hui
Ren, Xiubao
Zhang, Hongbing
Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis
title Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis
title_full Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis
title_fullStr Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis
title_full_unstemmed Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis
title_short Phosphoglyceric acid mutase-1 contributes to oncogenic mTOR-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis
title_sort phosphoglyceric acid mutase-1 contributes to oncogenic mtor-mediated tumor growth and confers non-small cell lung cancer patients with poor prognosis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5988759/
https://www.ncbi.nlm.nih.gov/pubmed/29362480
http://dx.doi.org/10.1038/s41418-017-0034-y
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