The methionine cycle and its cancer implications

IF 6.9 1区医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY

Oncogene Pub Date : 2024-10-11 DOI:10.1038/s41388-024-03122-0

Valentina Tassinari, Wei Jia, Wen-Lian Chen, Eleonora Candi, Gerry Melino

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Abstract

The essential amino acid methionine is a crucial regulator of sulfur metabolism in a variety of interconnected biochemical pathways. The methionine cycle is intricately linked to the folate cycle, forming the one-carbon metabolism, a crucial regulator of S-adenosylmethionine, SAM. Recent work highlights methionine’s critical role in tumor growth and progression, maintaining polyamine synthesis, and playing a crucial role in the regulation of SAM both in altered chromatin states, depending on p53 status, as well as facilitating m6A methylation of NR4A2 mRNA, hence regulating proliferation in esophageal carcinoma. Accordingly, Celecoxib, a specific NR4A2 inhibitor, is a potentially powerful inhibitor of tumor growth at least in this specific model. Additionally, formaldehyde, from endogenous or exogenous sources, can directly regulate both SAM steady-state-levels and the one-carbon metabolism, with relevant implication in cancer progression. These recent scientific advancements have provided a deeper understanding of the molecular mechanisms involved in cancer development, and its potential therapeutic regulation.

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蛋氨酸循环及其对癌症的影响。

在各种相互关联的生化途径中，必需氨基酸蛋氨酸是硫代谢的重要调节剂。蛋氨酸循环与叶酸循环错综复杂地联系在一起，形成一碳代谢，是 S-腺苷蛋氨酸（SAM）的重要调节因子。最近的研究强调了蛋氨酸在肿瘤生长和进展过程中的关键作用，它能维持多胺的合成，并根据 p53 状态在染色质状态的改变中对 SAM 的调节发挥关键作用，还能促进 NR4A2 mRNA 的 m6A 甲基化，从而调节食管癌的增殖。因此，至少在这一特定模型中，NR4A2 的特异性抑制剂塞来昔布可能是一种强有力的肿瘤生长抑制剂。此外，来自内源性或外源性的甲醛可直接调节 SAM 稳态水平和一碳代谢，并对癌症进展产生相关影响。这些最新的科学进展让人们对癌症发展的分子机制及其潜在的治疗调节有了更深入的了解。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Oncogene 医学-生化与分子生物学

CiteScore

15.30

自引率

1.20%

发文量

404

审稿时长

1 months

期刊介绍： Oncogene is dedicated to advancing our understanding of cancer processes through the publication of exceptional research. The journal seeks to disseminate work that challenges conventional theories and contributes to establishing new paradigms in the etio-pathogenesis, diagnosis, treatment, or prevention of cancers. Emphasis is placed on research shedding light on processes driving metastatic spread and providing crucial insights into cancer biology beyond existing knowledge. Areas covered include the cellular and molecular biology of cancer, resistance to cancer therapies, and the development of improved approaches to enhance survival. Oncogene spans the spectrum of cancer biology, from fundamental and theoretical work to translational, applied, and clinical research, including early and late Phase clinical trials, particularly those with biologic and translational endpoints.