| 张晓斐,刘沛宜,梅国松,等.单羧酸转运蛋白的肿瘤临床应用进展[J].肿瘤学杂志,2024,30(10):866-873. |
| 单羧酸转运蛋白的肿瘤临床应用进展 |
| Progress in Clinical Application of Monocarboxylate Transporters in Tumors |
| 投稿时间：2024-06-20 |
| DOI：10.11735/j.issn.1671-170X.2024.10.B011 |
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| 中文关键词: 糖酵解 乳酸 单羧酸转运蛋白 肿瘤治疗 |
| 英文关键词:glycolysis lactic acid monocarboxylate transporter oncology treatment |
| 基金项目:新疆维吾尔族自治区自然科学基金资助项目（2021D01C027）；国家自然科学基金资助项目（82303695）；北京市希思科临床肿瘤学研究基金会（HYXH2023070）；吴阶平医学基金会临床科研专项资助基金（32067502022-22-53） |
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| 摘要点击次数: 96 |
| 全文下载次数: 35 |
| 中文摘要: |
| 摘 要：肿瘤细胞由于存在代谢重编程的特性表现出高糖酵解率，导致乳酸过量产生以及细胞外酸度增加。单羧酸转运蛋白（monocarboxylate transporter，MCT ）通过介导跨细胞膜的质子耦合乳酸转运，对维持这种代谢表型至关重要，也有助于肿瘤细胞pH值调节。溶质载体16（solute carrier 16，SLC16）基因家族编码的蛋白质MCT1和MCT4亚型在实体瘤和血液恶性肿瘤等多种肿瘤中过度表达。与特定生理环境中发生的情况类似，MCT1和MCT4能够介导肿瘤细胞之间以及肿瘤微环境中的肿瘤和基质细胞之间的乳酸穿梭。这种形式的代谢合作方式是引起多种重要的肿瘤侵袭性特征的原因，包括细胞增殖、存活、血管生成、迁移、侵袭、转移、免疫耐受和治疗抵抗。对MCT功能调节了解的日益深入为临床实践中可预见的新型抑制剂的设计提供了新途径。全文概述MCT亚型在肿瘤中的作用，总结其药理学靶向的最新进展，以及新型有效的选择性MCT1和/或MCT4抑制剂在肿瘤治疗中的潜力。 |
| 英文摘要: |
| Abstract： Tumor cells exhibit high rates of glycolysis due to the presence of metabolic reprogramming， resulting in excessive lactate production as well as increased extracellular acidity. Proton-linked monocarboxylate transporter(MCT) are essential for maintaining this metabolic phenotype by mediating proton-coupled lactate transport across cell membranes and also contribute to tumor cell pH regulation. Among the proteins encoded by the SLC16 gene family， the MCT1 and MCT4 subtypes are the most studied in tumors， and they are overexpressed in a variety of tumor types， such as solid tumors and hematologic malignancies. Similar to what occurs in specific physiological environments， MCT1 and MCT4 are able to mediate lactate shuttling between tumor cells and between tumor and stromal cells in the tumor microenvironment. This form of metabolic cooperative mode is responsible for important tumor aggressive features， including cell proliferation， survival， angiogenesis， migration， invasion， metastasis， immune tolerance， and treatment resistance. The growing understanding of the functional regulation of MCTs provides a new avenue for the design of novel inhibitors that are foreseeable in clinical practice. This review provides an overview of the role of MCT subtypes in tumors， summarizes recent advances in their pharmacological targeting， and summarizes the potential of novel potent and selective MCT1 and/or MCT4 inhibitors in cancer therapy. |
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