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单羧酸转运蛋白1(MCT1)在肿瘤进展和靶向治疗中的作用:综述

The role of MCT1 in tumor progression and targeted therapy: a comprehensive review.

作者信息

Xu Zheng, Wang Xuemei, Cheng Hongjing, Li Jiuling, Zhang Xin, Wang Xueju

机构信息

Department of Pathology, China-Japan Union Hospital, Jilin University, Changchun, Jilin, China.

出版信息

Front Immunol. 2025 Jun 19;16:1610466. doi: 10.3389/fimmu.2025.1610466. eCollection 2025.

Abstract

Overexpression of monocarboxylate transporter 1 (MCT1) in tumor cells is often associated with poor prognosis. The established mechanisms through which MCT1 and its mediated lactate transport drive tumor progression are manifold. The classical mechanisms include fostering metabolic symbiosis among tumor cells, dampening the immune function of immune cells, and spurring tumor angiogenesis. Beyond these, new findings of MCT1's role in tumor progression have emerged. These new findings highlight MCT1's involvement in mediating the reverse Warburg effect, inhibiting ferroptosis, promoting protective autophagy, and augmenting tumor glycolysis. When acetate serves as a transport substrate for MCT1, additional mechanisms come into play. These encompass MCT1's participation in the acetylation of histone H3K27 and its role in upregulating c-Myc levels. Several studies have demonstrated that while selective MCT1 inhibitors can effectively impede tumor progression, they also face notable challenges. To address these, combining MCT1 inhibitors with other drugs appears to hold more promise.

摘要

肿瘤细胞中单羧酸转运蛋白1(MCT1)的过表达通常与不良预后相关。MCT1及其介导的乳酸转运驱动肿瘤进展的既定机制是多方面的。经典机制包括促进肿瘤细胞之间的代谢共生、抑制免疫细胞的免疫功能以及刺激肿瘤血管生成。除此之外,MCT1在肿瘤进展中的作用也有了新发现。这些新发现突出了MCT1在介导逆向Warburg效应、抑制铁死亡、促进保护性自噬以及增强肿瘤糖酵解中的作用。当乙酸盐作为MCT1的转运底物时,会发挥其他机制。这些机制包括MCT1参与组蛋白H3K27的乙酰化及其在上调c-Myc水平中的作用。多项研究表明,虽然选择性MCT1抑制剂可以有效阻碍肿瘤进展,但它们也面临着显著挑战。为了解决这些问题,将MCT1抑制剂与其他药物联合使用似乎更有前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfb4/12222217/982ae5b881ad/fimmu-16-1610466-g001.jpg

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