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Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth
Cancer cells often proliferate under hypoxia and reprogram their metabolism. However, how to find targets to effectively block the hypoxia-associated metabolic pathways remains unclear. Here, we developed a tool to conveniently calculate electrons dissipated in metabolic transformations. Based on th...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Rockefeller University Press
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062513/ https://www.ncbi.nlm.nih.gov/pubmed/31961917 http://dx.doi.org/10.1084/jem.20191226 |
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author | Liu, Miao Wang, Yuanyuan Yang, Chuanzhen Ruan, Yuxia Bai, Changsen Chu, Qiaoyun Cui, Yanfen Chen, Ceshi Ying, Guoguang Li, Binghui |
author_facet | Liu, Miao Wang, Yuanyuan Yang, Chuanzhen Ruan, Yuxia Bai, Changsen Chu, Qiaoyun Cui, Yanfen Chen, Ceshi Ying, Guoguang Li, Binghui |
author_sort | Liu, Miao |
collection | PubMed |
description | Cancer cells often proliferate under hypoxia and reprogram their metabolism. However, how to find targets to effectively block the hypoxia-associated metabolic pathways remains unclear. Here, we developed a tool to conveniently calculate electrons dissipated in metabolic transformations. Based on the law of conservation of electrons in chemical reactions, we further built up an electron balance model for central carbon metabolism, and it can accurately outline metabolic plasticity under hypoxia. Our model specifies that glutamine metabolism reprogrammed for biosynthesis of lipid and/or proline actually acts as the alternative electron bin to enable electron transfer in proliferating cells under hypoxia. Inhibition of both proline biosynthesis and lipogenesis can synergistically suppress cancer cell growth under hypoxia and in vivo tumor onset. Therefore, our model helps to reveal combinations of potential targets to inhibit tumor growth by blocking hypoxia-rewired metabolism and provides a useful tool for future studies on cancer metabolism. |
format | Online Article Text |
id | pubmed-7062513 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | Rockefeller University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-70625132020-09-02 Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth Liu, Miao Wang, Yuanyuan Yang, Chuanzhen Ruan, Yuxia Bai, Changsen Chu, Qiaoyun Cui, Yanfen Chen, Ceshi Ying, Guoguang Li, Binghui J Exp Med Article Cancer cells often proliferate under hypoxia and reprogram their metabolism. However, how to find targets to effectively block the hypoxia-associated metabolic pathways remains unclear. Here, we developed a tool to conveniently calculate electrons dissipated in metabolic transformations. Based on the law of conservation of electrons in chemical reactions, we further built up an electron balance model for central carbon metabolism, and it can accurately outline metabolic plasticity under hypoxia. Our model specifies that glutamine metabolism reprogrammed for biosynthesis of lipid and/or proline actually acts as the alternative electron bin to enable electron transfer in proliferating cells under hypoxia. Inhibition of both proline biosynthesis and lipogenesis can synergistically suppress cancer cell growth under hypoxia and in vivo tumor onset. Therefore, our model helps to reveal combinations of potential targets to inhibit tumor growth by blocking hypoxia-rewired metabolism and provides a useful tool for future studies on cancer metabolism. Rockefeller University Press 2020-01-21 /pmc/articles/PMC7062513/ /pubmed/31961917 http://dx.doi.org/10.1084/jem.20191226 Text en © 2020 Liu et al. http://www.rupress.org/terms/https://creativecommons.org/licenses/by-nc-sa/4.0/This article is distributed under the terms of an Attribution–Noncommercial–Share Alike–No Mirror Sites license for the first six months after the publication date (see http://www.rupress.org/terms/). After six months it is available under a Creative Commons License (Attribution–Noncommercial–Share Alike 4.0 International license, as described at https://creativecommons.org/licenses/by-nc-sa/4.0/). |
spellingShingle | Article Liu, Miao Wang, Yuanyuan Yang, Chuanzhen Ruan, Yuxia Bai, Changsen Chu, Qiaoyun Cui, Yanfen Chen, Ceshi Ying, Guoguang Li, Binghui Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth |
title | Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth |
title_full | Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth |
title_fullStr | Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth |
title_full_unstemmed | Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth |
title_short | Inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth |
title_sort | inhibiting both proline biosynthesis and lipogenesis synergistically suppresses tumor growth |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7062513/ https://www.ncbi.nlm.nih.gov/pubmed/31961917 http://dx.doi.org/10.1084/jem.20191226 |
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