A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer

Glucose metabolism is remodeled in cancer, but the global pattern of cancer-specific metabolic changes remains unclear. Here we show, using the comprehensive measurement of metabolic enzymes by large-scale targeted proteomics, that the metabolism both carbon and nitrogen is altered during the malign...

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Autores principales: Kodama, Manabu, Oshikawa, Kiyotaka, Shimizu, Hideyuki, Yoshioka, Susumu, Takahashi, Masatomo, Izumi, Yoshihiro, Bamba, Takeshi, Tateishi, Chisa, Tomonaga, Takeshi, Matsumoto, Masaki, Nakayama, Keiichi I.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2020
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078194/
https://www.ncbi.nlm.nih.gov/pubmed/32184390
http://dx.doi.org/10.1038/s41467-020-15136-9
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author Kodama, Manabu
Oshikawa, Kiyotaka
Shimizu, Hideyuki
Yoshioka, Susumu
Takahashi, Masatomo
Izumi, Yoshihiro
Bamba, Takeshi
Tateishi, Chisa
Tomonaga, Takeshi
Matsumoto, Masaki
Nakayama, Keiichi I.
author_facet Kodama, Manabu
Oshikawa, Kiyotaka
Shimizu, Hideyuki
Yoshioka, Susumu
Takahashi, Masatomo
Izumi, Yoshihiro
Bamba, Takeshi
Tateishi, Chisa
Tomonaga, Takeshi
Matsumoto, Masaki
Nakayama, Keiichi I.
author_sort Kodama, Manabu
collection PubMed
description Glucose metabolism is remodeled in cancer, but the global pattern of cancer-specific metabolic changes remains unclear. Here we show, using the comprehensive measurement of metabolic enzymes by large-scale targeted proteomics, that the metabolism both carbon and nitrogen is altered during the malignant progression of cancer. The fate of glutamine nitrogen is shifted from the anaplerotic pathway into the TCA cycle to nucleotide biosynthesis, with this shift being controlled by glutaminase (GLS1) and phosphoribosyl pyrophosphate amidotransferase (PPAT). Interventions to reduce the PPAT/GLS1 ratio suppresses tumor growth of many types of cancer. A meta-analysis reveals that PPAT shows the strongest correlation with malignancy among all metabolic enzymes, in particular in neuroendocrine cancer including small cell lung cancer (SCLC). PPAT depletion suppresses the growth of SCLC lines. A shift in glutamine fate may thus be required for malignant progression of cancer, with modulation of nitrogen metabolism being a potential approach to SCLC treatment.
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spelling pubmed-70781942020-03-19 A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer Kodama, Manabu Oshikawa, Kiyotaka Shimizu, Hideyuki Yoshioka, Susumu Takahashi, Masatomo Izumi, Yoshihiro Bamba, Takeshi Tateishi, Chisa Tomonaga, Takeshi Matsumoto, Masaki Nakayama, Keiichi I. Nat Commun Article Glucose metabolism is remodeled in cancer, but the global pattern of cancer-specific metabolic changes remains unclear. Here we show, using the comprehensive measurement of metabolic enzymes by large-scale targeted proteomics, that the metabolism both carbon and nitrogen is altered during the malignant progression of cancer. The fate of glutamine nitrogen is shifted from the anaplerotic pathway into the TCA cycle to nucleotide biosynthesis, with this shift being controlled by glutaminase (GLS1) and phosphoribosyl pyrophosphate amidotransferase (PPAT). Interventions to reduce the PPAT/GLS1 ratio suppresses tumor growth of many types of cancer. A meta-analysis reveals that PPAT shows the strongest correlation with malignancy among all metabolic enzymes, in particular in neuroendocrine cancer including small cell lung cancer (SCLC). PPAT depletion suppresses the growth of SCLC lines. A shift in glutamine fate may thus be required for malignant progression of cancer, with modulation of nitrogen metabolism being a potential approach to SCLC treatment. Nature Publishing Group UK 2020-03-17 /pmc/articles/PMC7078194/ /pubmed/32184390 http://dx.doi.org/10.1038/s41467-020-15136-9 Text en © The Author(s) 2020 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
Kodama, Manabu
Oshikawa, Kiyotaka
Shimizu, Hideyuki
Yoshioka, Susumu
Takahashi, Masatomo
Izumi, Yoshihiro
Bamba, Takeshi
Tateishi, Chisa
Tomonaga, Takeshi
Matsumoto, Masaki
Nakayama, Keiichi I.
A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer
title A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer
title_full A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer
title_fullStr A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer
title_full_unstemmed A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer
title_short A shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer
title_sort shift in glutamine nitrogen metabolism contributes to the malignant progression of cancer
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7078194/
https://www.ncbi.nlm.nih.gov/pubmed/32184390
http://dx.doi.org/10.1038/s41467-020-15136-9
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