Rho Hyunsoo, Hay Nissim
Department of Biochemistry and Molecular Genetics, College of Medicine, University of Illinois at Chicago, Chicago, IL, USA.
College of Pharmacy, Graduate School of Pharmaceutical Sciences, Ewha Womans University, Seoul, Republic of Korea.
Exp Mol Med. 2025 Mar;57(3):545-553. doi: 10.1038/s12276-025-01410-7. Epub 2025 Mar 24.
Increased glycolysis, which leads to high lactate production, is a common feature of cancer cells. Recent evidence suggests that lactate plays a role in the post-translational modification of histone and nonhistone proteins via lactylation. In contrast to genetic mutations, lactylation in cancer cells is reversible. Thus, reversing lactylation can be exploited as a pharmacological intervention for various cancers. Here we discuss recent advances in histone and nonhistone lactylation in cancer, including L-, D- and S-lactylation, as well as alanyl-tRNA synthetase as a novel lactyltransferase. We also discuss potential approaches for targeting lactylation as a therapeutic opportunity in cancer treatment.
糖酵解增加会导致乳酸大量生成，这是癌细胞的一个共同特征。最近的证据表明，乳酸通过乳酰化作用参与组蛋白和非组蛋白的翻译后修饰。与基因突变不同，癌细胞中的乳酰化是可逆的。因此，逆转乳酰化可作为针对各种癌症的一种药物干预手段。在此，我们讨论癌症中组蛋白和非组蛋白乳酰化的最新进展，包括L-、D-和S-乳酰化，以及作为一种新型乳酰转移酶的丙氨酰-tRNA合成酶。我们还讨论了将靶向乳酰化作为癌症治疗中的一种治疗机会的潜在方法。
