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乳酸盐:代谢与免疫抑制的中介物。

Lactate: The Mediator of Metabolism and Immunosuppression.

机构信息

The First Affiliated Hospital of Gannan Medical University, Ganzhou, China.

Key Laboratory of Prevention and Treatment of Cardiovascular and Cerebrovascular Diseases of Ministry of Education, Gannan Medical University, Ganzhou, China.

出版信息

Front Endocrinol (Lausanne). 2022 Jun 9;13:901495. doi: 10.3389/fendo.2022.901495. eCollection 2022.

Abstract

The Warburg effect, one of the hallmarks of tumors, produces large amounts of lactate and generates an acidic tumor microenvironment using glucose for glycolysis. As a metabolite, lactate not only serves as a substrate to provide energy for supporting cell growth and development but also acts as an important signal molecule to affect the biochemical functions of intracellular proteins and regulate the biological functions of different kinds of cells. Notably, histone lysine lactylation (Kla) is identified as a novel post-modification and carcinogenic signal, which provides the promising and potential therapeutic targets for tumors. Therefore, the metabolism and functional mechanism of lactate are becoming one of the hot fields in tumor research. Here, we review the production of lactate and its regulation on immunosuppressive cells, as well as the important role of Kla in hepatocellular carcinoma. Lactate and Kla supplement the knowledge gap in oncology and pave the way for exploring the mechanism of oncogenesis and therapeutic targets. Research is still needed in this field.

摘要

瓦博格效应(Warburg effect)是肿瘤的标志之一,它利用葡萄糖进行糖酵解产生大量乳酸,并生成酸性肿瘤微环境。作为一种代谢产物,乳酸不仅可以作为提供能量的底物,支持细胞生长和发育,还可以作为一种重要的信号分子,影响细胞内蛋白质的生化功能,调节各种细胞的生物学功能。值得注意的是,组蛋白赖氨酸乳酸化(Kla)被鉴定为一种新的翻译后修饰和致癌信号,为肿瘤提供了有前途和潜在的治疗靶点。因此,乳酸的代谢和功能机制正成为肿瘤研究的热点领域之一。在这里,我们综述了乳酸的产生及其对免疫抑制细胞的调节作用,以及 Kla 在肝细胞癌中的重要作用。乳酸和 Kla 填补了肿瘤学知识空白,为探索致癌机制和治疗靶点铺平了道路。该领域仍需要进一步研究。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/6c5e/9218951/fd6f3d467cac/fendo-13-901495-g001.jpg

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