期刊
JOURNAL FOR IMMUNOTHERAPY OF CANCER
卷 9, 期 2, 页码 -出版社
BMJ PUBLISHING GROUP
DOI: 10.1136/jitc-2020-001364
关键词
tumor microenvironment; tumor escape; macrophages; immunomodulation; immune evation
资金
- National Nature Science Foundation of China [81972213, 81702388, 81802503, 81 772 180]
- Key University Science Research Project of Anhui Province [KJ2020A0594, 1808085MH271]
- Shanghai Training and Support Program for Young Physician
- Fudan University Shanghai Cancer Center for Outstanding Youth Scholars Foundation [YJYQ201803]
- Shanghai Sailing Program [18YF1412700]
- Peak Training Program for Scientific Research of Yijishan Hospital, Wannan Medical College [GF2019T01, GF2019G15]
The study revealed that in TAMs in gastric cancer patients, increased levels of MAT2A play a role in the activation and maintenance of TAMs phenotype, mediating the upregulation of RIP1. This finding sheds light on the regulatory role of methionine metabolism in the anti-inflammatory function of monocytes in GC, with MAT2A potentially serving as a therapeutic target.
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.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据