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溶质载体作为潜在的癌基因或抑癌基因:它们在恶性肿瘤形成中的关键作用。

Solute carriers as potential oncodrivers or suppressors: their key functions in malignant tumor formation.

机构信息

Department of Medical Oncology, Zhongshan Hospital, Fudan University, Shanghai, China.

Department of Medical Biochemistry, College of Medicine, Shaqra University, Shaqra, Saudi Arabia.

出版信息

Drug Discov Today. 2021 Jul;26(7):1689-1701. doi: 10.1016/j.drudis.2021.03.004. Epub 2021 Mar 15.

Abstract

Solute carrier (SLC) transporters are primarily known for their function in the transportation of various exogenous/endogenous substances via influx/efflux mechanisms. In addition to their diverse role in several tumor-modulating functions, such as proliferation, migration, angiogenesis, epithelial-mesenchymal transition (EMT), epigenetic modification, chemoresistance, immunoregulation, and oncometabolism, influx/efflux-independent contributions of SLCs in the activation of various signaling network cascades that might drive metastatic tumor formation have also been uncovered. Disappointingly, even after two decades and the discovery of >450 SLCs, many of their members remain orphans in terms of cancer pathogenesis. In this review, we summarize the current understanding of the tumor-modulating functions, mechanisms, and complexity of SLCs, as well as their potential as targets for cancer therapy.

摘要

溶质载体 (SLC) 转运蛋白主要以其通过内流/外排机制运输各种外源性/内源性物质的功能而闻名。除了在多种肿瘤调节功能(如增殖、迁移、血管生成、上皮-间充质转化 (EMT)、表观遗传修饰、化疗耐药性、免疫调节和癌代谢)中发挥多样化作用外,SLC 还通过激活各种信号网络级联反应来促进肿瘤转移形成,这些级联反应与外排无关。令人失望的是,即使经过二十年的时间,发现了 >450 种 SLC,它们中的许多成员在癌症发病机制方面仍然是孤儿。在这篇综述中,我们总结了 SLC 的肿瘤调节功能、机制和复杂性的最新认识,以及它们作为癌症治疗靶点的潜力。

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