Deng Dan, Luo Yan, Hong Yun, Ren Xing, Zu Xuyu, Feng Jianbo
The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China; Clinical Laboratory Medicine Center, The First Affiliated Hospital of University of South China, Hengyang 421001, Hunan, China.
The First Affiliated Hospital, Cancer Research Institute, Hengyang Medical School, University of South China, Hengyang, 421001, Hunan, China.
Biochim Biophys Acta Rev Cancer. 2025 Oct;1880(5):189399. doi: 10.1016/j.bbcan.2025.189399. Epub 2025 Jul 30.
Lactate, a central metabolite generated during glycolysis, functions not only as a by-product but also as a critical signalling mediator, profoundly influencing tumor progression and cellular destiny. Among the post-translational modifications, lactylation-a novel modification driven by lactate-has emerged as a transformative discovery, reshaping our understanding of lactate's role within the tumor microenvironment (TME). This modification bridges metabolic reprogramming and epigenetic regulation, unveiling previously unexplored dimensions of tumor biology. Recent findings demonstrate that protein lactylation in tumor cells, cancer stem cells, and immune cells infiltrating the TME can modulate transcriptional activities, thereby influencing tumor initiation, progression, and immune evasion. These insights position lactylation as a promising target for new therapeutic strategies in cancer. This review expounds on the underlying mechanisms of lactylation, including the identification of the "writers" and "erasers" involved in protein lactylation, and highlights the physiological significance of lactylation across diverse biological contexts. Furthermore, the paper emphasized on the latest advancements in understanding the modulatory functions of protein lactylation within pathological processes, the potential for targeting lactylation sites, and underscores the scientific significance for future investigative endeavours.
乳酸是糖酵解过程中产生的一种核心代谢物，它不仅作为一种副产物发挥作用，还作为一种关键的信号介质，深刻影响肿瘤进展和细胞命运。在翻译后修饰中，乳酸化——一种由乳酸驱动的新型修饰——已成为一项变革性发现，重塑了我们对乳酸在肿瘤微环境（TME）中作用的理解。这种修饰连接了代谢重编程和表观遗传调控，揭示了肿瘤生物学中以前未被探索的维度。最近的研究结果表明，肿瘤细胞、癌症干细胞以及浸润到TME中的免疫细胞中的蛋白质乳酸化可以调节转录活性，从而影响肿瘤的发生、进展和免疫逃逸。这些见解将乳酸化定位为癌症新治疗策略的一个有前景的靶点。本综述阐述了乳酸化的潜在机制，包括参与蛋白质乳酸化的“书写者”和“擦除者”的鉴定，并强调了乳酸化在不同生物学背景下的生理意义。此外，本文还强调了在理解蛋白质乳酸化在病理过程中的调节功能方面的最新进展、靶向乳酸化位点的潜力，并强调了未来研究工作的科学意义。
