蛋氨酸
甲基化
生物
癌症研究
细胞周期
癌基因
细胞生物学
细胞
基因
生物化学
氨基酸
作者
Xing Jin,Lei Liu,Dan Liŭ,Junbiao Wu,Congcong Wang,Siliang Wang,Fengying Wang,Guanzhen Yu,Xinqiao Jin,Yingwei Xue,Dan Jiang,Yan Ni,Xi Yang,Ming-Song Wang,Zhiwei Wang,Yuriy L. Orlov,Jia Wang,Gerry Melino,Ji‐Bin Liu,Wen‐Lian Chen
标识
DOI:10.1038/s41418-024-01285-7
摘要
Esophageal squamous cell carcinoma (ESCC) is a deadly malignancy with notable metabolic reprogramming, yet the pivotal metabolic feature driving ESCC progression remains elusive. Here, we show that methionine cycle exhibits robust activation in ESCC and is reversely associated with patient survival. ESCC cells readily harness exogenous methionine to generate S-adenosyl-methionine (SAM), thus promoting cell proliferation. Mechanistically, methionine augments METTL3-mediated RNA m6A methylation through SAM and revises gene expression. Integrative omics analysis highlights the potent influence of methionine/SAM on NR4A2 expression in a tumor-specific manner, mediated by the IGF2BP2-dependent stabilization of methylated NR4A2 mRNA. We demonstrate that NR4A2 facilitates ESCC growth and negatively impacts patient survival. We further identify celecoxib as an effective inhibitor of NR4A2, offering promise as a new anti-ESCC agent. In summary, our findings underscore the active methionine cycle as a critical metabolic characteristic in ESCC, and pinpoint NR4A2 as a novel methionine-responsive oncogene, thereby presenting a compelling target potentially superior to methionine restriction.
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