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超越代谢废物:赖氨酸酰化及其在癌症进展和细胞命运决定中的潜在作用。

Beyond metabolic waste: lysine lactylation and its potential roles in cancer progression and cell fate determination.

机构信息

Department of Stem Cell and Regenerative Medicine, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China.

International Joint Research Center for Precision Biotherapy, Ministry of Science and Technology, Southwest Hospital, Third Military Medical University (Army Medical University), 400038, Chongqing, China.

出版信息

Cell Oncol (Dordr). 2023 Jun;46(3):465-480. doi: 10.1007/s13402-023-00775-z. Epub 2023 Jan 19.

Abstract

BACKGROUND

Lactate is an important metabolite derived from glycolysis under physiological and pathological conditions. The Warburg effect reveals the vital role of lactate in cancer progression. Numerous studies have reported crucial roles for lactate in cancer progression and cell fate determination. Lactylation, a novel posttranslational modification (PTM), has provided a new opportunity to investigate metabolic epigenetic regulation, and studies of this process have been initiated in a wide range of cancer cells, cancer-associated immune cells, and embryonic stem cells.

CONCLUSION

Lactylation is a novel and interesting mechanism of lactate metabolism linked to metabolic rewiring and epigenetic remodeling. It is a potential and hopeful target for cancer therapy. Here, we summarize the discovery of lactylation, the mechanisms of site modification, and progress in research on nonhistone lactylation. We focus on the potential roles of lactylation in cancer progression and cell fate determination and the possible therapeutic strategies for targeting lysine lactylation. Finally, we suggest some future research topics on lactylation to inspire some interesting ideas.

摘要

背景

乳酸是生理和病理条件下糖酵解的重要代谢产物。沃伯格效应揭示了乳酸在癌症进展中的重要作用。大量研究报道了乳酸在癌症进展和细胞命运决定中的关键作用。乳酰化,一种新的翻译后修饰(PTM),为代谢表观遗传调控的研究提供了新的机会,并且这一过程的研究已经在广泛的癌细胞、癌症相关免疫细胞和胚胎干细胞中展开。

结论

乳酰化是一种与代谢重排和表观遗传重塑相关的新型有趣的乳酸代谢机制。它是癌症治疗的一个有潜力和有希望的靶点。在这里,我们总结了乳酰化的发现、修饰位点的机制以及非组蛋白乳酰化研究的进展。我们重点关注乳酰化在癌症进展和细胞命运决定中的潜在作用,以及针对赖氨酸乳酰化的可能治疗策略。最后,我们提出了一些关于乳酰化的未来研究课题,以激发一些有趣的想法。

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