Department of Urology, Renmin Hospital of Wuhan University, Wuhan, Hubei, P.R. China.
Clin Transl Med. 2024 Nov;14(11):e70070. doi: 10.1002/ctm2.70070.
Lactylation, a recently identified form of protein post-translational modification (PTM), has emerged as a key player in cancer biology. The Warburg effect, a hallmark of tumour metabolism, underscores the significance of lactylation in cancer progression. By regulating gene transcription and protein function, lactylation facilitates metabolic reprogramming, enabling tumours to adapt to nutrient limitations and sustain rapid growth. Over the past decade, extensive research has revealed the intricate regulatory network underlying lactylation in tumours. Large-scale sequencing and machine learning have confirmed the widespread occurrence of lactylation sites across the tumour proteome. Targeting lactylation enzymes or metabolic pathways has demonstrated promising anti-tumour effects, highlighting the therapeutic potential of this modification. This review comprehensively explores the mechanisms of lactylation in cancer cells and the tumour microenvironment. We expound on the application of advanced omics technologies for target identification and data modelling within the lactylation field. Additionally, we summarise existing anti-lactylation drugs and discuss their clinical implications. By providing a comprehensive overview of recent advancements, this review aims to stimulate innovative research and accelerate the translation of lactylation-based therapies into clinical practice. KEY POINTS: Lactylation significantly influences tumour metabolism and gene regulation, contributing to cancer progression. Advanced sequencing and machine learning reveal widespread lactylation sites in tumours. Targeting lactylation enzymes shows promise in enhancing anti-tumour drug efficacy and overcoming chemotherapy resistance. This review outlines the clinical implications and future research directions of lactylation in oncology.
乳酰化作用，一种新发现的蛋白质翻译后修饰（PTM）形式，已成为癌症生物学的关键因素。肿瘤代谢的标志——沃伯格效应，强调了乳酰化作用在癌症进展中的重要性。通过调节基因转录和蛋白质功能，乳酰化作用促进了代谢重编程，使肿瘤能够适应营养限制并维持快速生长。在过去的十年中，大量研究揭示了肿瘤中乳酰化作用的复杂调控网络。大规模测序和机器学习已经证实了乳酰化位点在肿瘤蛋白质组中的广泛存在。靶向乳酰化酶或代谢途径已显示出有希望的抗肿瘤效果，突出了这种修饰的治疗潜力。 本综述全面探讨了乳酰化作用在癌细胞和肿瘤微环境中的机制。我们详细阐述了先进的组学技术在乳酰化领域中的目标识别和数据建模的应用。此外，我们总结了现有的抗乳酰化药物，并讨论了它们的临床意义。通过全面概述最新进展，本综述旨在激发创新性研究，并加速基于乳酰化作用的治疗方法向临床实践的转化。 要点：乳酰化作用显著影响肿瘤代谢和基因调控，促进癌症进展。先进的测序和机器学习揭示了肿瘤中广泛存在的乳酰化位点。靶向乳酰化酶有望增强抗肿瘤药物的疗效并克服化疗耐药性。 本综述概述了乳酰化作用在肿瘤学中的临床意义和未来研究方向。
