Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer

Background The activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.Me...

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Autores principales:	Xi Yang, Yan Zhang, Hui Yang, Ping Wan, Ye Hu, YiRen Hu, Mingzhe Ma, Kun Lv
Formato:	article
Lenguaje:	EN
Publicado:	BMJ Publishing Group 2021
Materias:	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
Acceso en línea:	https://doaj.org/article/8b1d31c911d249e8a8a1ebbeec2cb156
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spelling	oai:doaj.org-article:8b1d31c911d249e8a8a1ebbeec2cb1562021-11-16T03:00:06ZActivation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer10.1136/jitc-2020-0013642051-1426https://doaj.org/article/8b1d31c911d249e8a8a1ebbeec2cb1562021-02-01T00:00:00Zhttps://jitc.bmj.com/content/9/2/e001364.fullhttps://doaj.org/toc/2051-1426Background The activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.Methods Monocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.Results TAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.Conclusions Our data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.Xi YangYan ZhangHui YangPing WanYe HuYiRen HuMingzhe MaKun LvBMJ Publishing GrouparticleNeoplasms. Tumors. Oncology. Including cancer and carcinogensRC254-282ENJournal for ImmunoTherapy of Cancer, Vol 9, Iss 2 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282
spellingShingle	Neoplasms. Tumors. Oncology. Including cancer and carcinogens RC254-282 Xi Yang Yan Zhang Hui Yang Ping Wan Ye Hu YiRen Hu Mingzhe Ma Kun Lv Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer
description	Background The activation of tumor-associated macrophages (TAMs) facilitates the progression of gastric cancer (GC). Cell metabolism reprogramming has been shown to play a vital role in the polarization of TAMs. However, the role of methionine metabolism in function of TAMs remains to be explored.Methods Monocytes/macrophages were isolated from peripheral blood, tumor tissues or normal tissues from healthy donors or patients with GC. The role of methionine metabolism in the activation of TAMs was evaluated with both in vivo analyses and in vitro experiments. Pharmacological inhibition of the methionine cycle and modulation of key metabolic genes was employed, where molecular and biological analyses were performed.Results TAMs have increased methionine cycle activity that are mainly attributed to elevated methionine adenosyltransferase II alpha (MAT2A) levels. MAT2A modulates the activation and maintenance of the phenotype of TAMs and mediates the upregulation of RIP1 by increasing the histone H3K4 methylation (H3K4me3) at its promoter regions.Conclusions Our data cast light on a novel mechanism by which methionine metabolism regulates the anti-inflammatory functions of monocytes in GC. MAT2A might be a potential therapeutic target for cancer cells as well as TAMs in GC.
format	article
author	Xi Yang Yan Zhang Hui Yang Ping Wan Ye Hu YiRen Hu Mingzhe Ma Kun Lv
author_facet	Xi Yang Yan Zhang Hui Yang Ping Wan Ye Hu YiRen Hu Mingzhe Ma Kun Lv
author_sort	Xi Yang
title	Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer
title_short	Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer
title_full	Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer
title_fullStr	Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer
title_full_unstemmed	Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer
title_sort	activation of mat2a-rip1 signaling axis reprograms monocytes in gastric cancer
publisher	BMJ Publishing Group
publishDate	2021
url	https://doaj.org/article/8b1d31c911d249e8a8a1ebbeec2cb156
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Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer

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