乳酸化修饰在癌症中的研究进展

Role and Mechanism of Lactylation in Cancer

蛋白质的翻译后修饰(post-translational modifications,PTMs)可通过在前体蛋白的氨基酸残基上添加化学基团来改变其结构和功能,在信号转导、表观遗传和疾病等过程中发挥重要作用。乳酸化修饰(lactylation)是一种新发现的PTM,由于其与糖酵解代谢终产物乳酸密切相关,为理解细胞代谢重编程和表观遗传调控之间的联系提供了新视角。研究表明乳酸化修饰在肿瘤进展中发挥重要作用,并与临床不良预后相关。组蛋白的乳酸化异常可以影响肿瘤细胞和免疫细胞中的基因表达,从而进一步调控肿瘤的进展和免疫抑制。非组蛋白的乳酸化也可以调节肿瘤的增殖和耐药等过程。本文对乳酸化修饰领域的最新研究进展及其在肿瘤发生发展、微环境和免疫抑制中的作用和机制进行综述,并对其在肿瘤靶向治疗及联合免疫治疗方面的应用价值进行探讨。

Post translational modifications(PTMs)can change the properties of a protein by covalent addition of functional groups to one or more amino acids,and influence almost all aspects of normal cell biology and pathogenesis.Lactylation is a novel identified PTM,and has been found in both histone and non-histone proteins.Since associated with the end product of glycolysis--lactate,lactylation modification could provide a new perspective for understanding the relationship between metabolic reprogramming and epigenetic modifications.Accumulated evidences suggest that lactylation play important roles in tumor progression and links to poor prognosis in clinical studies.Histone lactylation can affect gene expression in tumor cells and immunological cells,further promoting tumor progression and immune suppression.Lactylation on non-histone proteins can also regulate tumor progression and drug resistance.In this review,we aimed to summarize the roles of lactylation in cancer progression,microenvironment interactions and immune suppression,try to identify new molecular targets for cancer therapy and provide a new direction for combined targeted therapy and immunotherapy.