乳酸不仅是糖酵解的终点产物，还逐渐被发现通过“乳酸运输”的方式在细胞之间发挥通用代谢燃料的作用，从而提供能量。在肿瘤和快速生长的细胞中发现了依赖糖酵解的代谢，这使得乳酸成为能量代谢重编程中一个关键的参与者，使细胞能够在短时间内获得充足的能量。此外，乳酸还可以通过建立酸性肿瘤微环境、招募免疫细胞等方式为肿瘤发生提供有利条件；同时，最近发现的乳酸诱导脱乳酸酰化机制更进一步加强了乳酸产生、循环和利用在促癌机制中的作用。与其他表观遗传修饰一样，乳酸化可以修饰组蛋白蛋白质，改变染色质的空间构型，影响DNA的可及性，并调节相应基因的表达。此外，乳酸化程度与空间定位的乳酸浓度密不可分，从而在表观遗传学和代谢重编程之间建立了桥梁。在本文中，我们回顾乳酸在能量重编程中的重要作用，总结乳酸脱乳酸酰化在肿瘤发生中的最新研究成果，并尝试探索可在癌症治疗中杀二鸟的治疗策略。©2023作者，由北京干细胞和再生医学研究所和约翰威利及其子公司有限公司出版发行的《细胞增殖》杂志发表。

Lactate is not only an endpoint of glycolysis but is gradually being discovered to play the role of a universal metabolic fuel for energy via the 'lactate shuttle' moving between cells and transmitting signals. The glycolytic-dependent metabolism found in tumours and fast-growing cells has made lactate a pivotal player in energy metabolism reprogramming, which enables cells to obtain abundant energy in a short time. Moreover, lactate can provide favourable conditions for tumorigenesis by shaping the acidic tumour microenvironment, recruiting immune cells, etc. and the recently discovered lactate-induced lactylation moves even further on pro-tumorigenesis mechanisms of lactate production, circulation and utilization. As with other epigenetic modifications, lactylation can modify histone proteins to alter the spatial configuration of chromatin, affect DNA accessibility and regulate the expression of corresponding genes. What's more, the degree of lactylation is inseparable from the spatialized lactate concentration, which builds a bridge between epigenetics and metabolic reprogramming. Here, we review the important role of lactate in energy reprogramming, summarize the latest finding of lactylation in tumorigenesis and try to explore therapeutic strategies in oncotherapy that can kill two birds with one stone.© 2023 The Authors. Cell Proliferation published by Beijing Institute for Stem Cell and Regenerative Medicine and John Wiley & Sons Ltd.