Tan Siqi, Zhou Faxiao, Wu Xiaoming
Laboratory of Molecular Genetics of Aging & Tumor, Medical School, Kunming University of Science and Technology, Chenggong Campus, 727 South Jingming Road, Kunming 650500, China.
Int J Mol Sci. 2025 Jun 11;26(12):5583. doi: 10.3390/ijms26125583.
Lactate is a key oncometabolite that plays a critical role in modulating the behavior and function of both tumor cells and tumor-associated stromal cells within the tumor microenvironment (TME). Cancer-associated fibroblasts (CAFs), as essential stromal components, engage in dynamic crosstalk with tumor cells through lactate-mediated signaling pathways. Elevated lactate levels in the TME primarily originate from metabolic reprogramming in tumor cells and CAFs. Notably, tumor-derived lactate not only promotes basement membrane remodeling and epithelial-mesenchymal transition (EMT) in CAFs but also influences their functional phenotype. Conversely, CAF-secreted lactate significantly contributes to tumor progression. Therapeutic strategies targeting lactate transport and metabolism-particularly through the inhibition of monocarboxylate transporters (MCTs) and lactate dehydrogenase (LDH)-have emerged as promising approaches in cancer treatment. This review summarizes the multifaceted roles of lactate and lactylation, elucidates the molecular mechanisms underlying lactate-mediated tumor-CAF crosstalk, and explores potential therapeutic interventions targeting lactate metabolism and CAFs.
乳酸是一种关键的肿瘤代谢物，在调节肿瘤微环境（TME）中肿瘤细胞和肿瘤相关基质细胞的行为及功能方面发挥着关键作用。癌症相关成纤维细胞（CAF）作为重要的基质成分，通过乳酸介导的信号通路与肿瘤细胞进行动态相互作用。TME中乳酸水平升高主要源于肿瘤细胞和CAF的代谢重编程。值得注意的是，肿瘤衍生的乳酸不仅促进CAF中的基底膜重塑和上皮-间质转化（EMT），还影响其功能表型。相反，CAF分泌的乳酸对肿瘤进展有显著贡献。针对乳酸转运和代谢的治疗策略——特别是通过抑制单羧酸转运体（MCT）和乳酸脱氢酶（LDH）——已成为癌症治疗中有前景的方法。本综述总结了乳酸和乳酰化的多方面作用，阐明了乳酸介导的肿瘤-CAF相互作用的分子机制，并探讨了针对乳酸代谢和CAF的潜在治疗干预措施。
