Yang Pei-Wen, Jiao Ju-Ying, Chen Zhen, Zhu Xiao-Yan, Cheng Chien-Shan
Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Department of Integrative Oncology, Shanghai Cancer Center, Fudan University, Shanghai 200032, China; Department of Oncology, Shanghai Medical College, Fudan University, Shanghai 200032, China.
Biochim Biophys Acta Rev Cancer. 2022 Sep;1877(5):188793. doi: 10.1016/j.bbcan.2022.188793. Epub 2022 Sep 9.
Methionine adenosyltransferases (MATs) synthesize S-adenosylmethionine (SAM) from methionine, which provides methyl groups for DNA, RNA, protein, and lipid methylation. MATs play a critical role in cellular processes, including growth, proliferation, and differentiation, and have been implicated in tumour development and progression. The expression of MATs is altered in hepatobiliary and pancreatic (HBP) cancers, which serves as a rare biomarker for early diagnosis and prognosis prediction of HBP cancers. Independent of SAM depletion in cells, MATs are often dysregulated at the transcriptional, post-transcriptional, and post-translational levels. Dysregulation of MATs is involved in carcinogenesis, chemotherapy resistance, T cell exhaustion, activation of tumour-associated macrophages, cancer stemness, and activation of tumourigenic pathways. Targeting MATs both directly and indirectly is a potential therapeutic strategy. This review summarizes the dysregulations of MATs, their proposed mechanism, diagnostic and prognostic roles, and potential therapeutic effects in context of HBP cancers.
甲硫氨酸腺苷转移酶（MATs）以甲硫氨酸合成S-腺苷甲硫氨酸（SAM），SAM为DNA、RNA、蛋白质和脂质甲基化提供甲基基团。MATs在包括生长、增殖和分化在内的细胞过程中发挥关键作用，并与肿瘤的发生和发展有关。MATs的表达在肝胆胰（HBP）癌中发生改变，这是HBP癌早期诊断和预后预测的一种罕见生物标志物。独立于细胞内SAM耗竭之外，MATs在转录、转录后和翻译后水平上常常失调。MATs的失调参与致癌作用、化疗耐药、T细胞耗竭、肿瘤相关巨噬细胞激活、癌症干性以及致癌途径的激活。直接和间接靶向MATs是一种潜在的治疗策略。本综述总结了MATs在HBP癌中的失调情况、其推测机制、诊断和预后作用以及潜在治疗效果。
