Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer.
Activation of MAT2A-RIP1 signaling axis reprograms monocytes in gastric cancer.
复制标题
MAT2A-RIP1 信号轴的激活可重新编程胃癌中的单核细胞。
DOI：
10.1136/jitc-2020-001364
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发表时间：
2021-03
影响因子：
10.9
通讯作者：
Ma M
中科院分区：
文献类型：
--
作者：
Zhang Y;Yang H;Zhao J;Wan P;Hu Y;Lv K;Hu Y;Yang X;Ma M
肿瘤相关巨噬细胞（TAMs）的活化促进了胃癌（GC）的进展。细胞代谢重编程已被证明在TAM的极化中起着至关重要的作用。然而，甲硫氨酸代谢在TAMs功能中的作用仍有待探讨。从健康供体或GC患者的外周血、肿瘤组织或正常组织中分离单核细胞/巨噬细胞。通过体内分析和体外实验评价了蛋氨酸代谢在TAM活化中的作用。采用甲硫氨酸循环的药理学抑制和关键代谢基因的调节，其中进行分子和生物学分析。TAM具有增加的甲硫氨酸循环活性，这主要归因于升高的甲硫氨酸腺苷转移酶II α（MAT 2A）水平。MAT 2A调节TAM表型的激活和维持，并通过增加其启动子区域的组蛋白H3 K4甲基化（H3 K4 me 3）介导RIP 1的上调。我们的数据揭示了一种新的机制，蛋氨酸代谢调节单核细胞在GC中的抗炎功能。MAT 2A可能是胃癌治疗的潜在靶点。
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. 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. 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. 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.
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影响因子：
5.2
作者：
Mentch SJ;Locasale JW
通讯作者：
Locasale JW
影响因子：
29
作者：
Divakaruni AS;Hsieh WY;Minarrieta L;Duong TN;Kim KKO;Desousa BR;Andreyev AY;Bowman CE;Caradonna K;Dranka BP;Ferrick DA;Liesa M;Stiles L;Rogers GW;Braas D;Ciaraldi TP;Wolfgang MJ;Sparwasser T;Berod L;Bensinger SJ;Murphy AN
通讯作者：
Murphy AN
DOI：
10.1073/pnas.1720113115
发表时间：
2018-07-10
影响因子：
11.1
作者：
Pacella, Ilenia;Procaccini, Claudio;Piconese, Silvia
通讯作者：
Piconese, Silvia
影响因子：
8.8
作者：
Lecoeur, Herve;Prina, Eric;Spath, Gerald F.
通讯作者：
Spath, Gerald F.
影响因子：
32.4
作者：
Kimball, Andrew S.;Davis, Frank M.;Gallagher, Katherine A.
通讯作者：
Gallagher, Katherine A.