Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan; Education Research Center for Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Hokkaido University, Japan.
Laboratory of Clinical Pharmaceutics & Therapeutics, Division of Pharmasciences, Faculty of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan.
Pharmacol Ther. 2021 Oct;226:107862. doi: 10.1016/j.pharmthera.2021.107862. Epub 2021 Apr 22.
Human monocarboxylate transporter 1 (hMCT1) and 4 (hMCT4) are involved in the proton-dependent transport of monocarboxylates such as L-lactate, which play an essential role in cellular metabolism and pH regulation. hMCT1 and 4 are overexpressed in a number of cancers, and polymorphisms in hMCT1 have been reported to be associated with the prognosis of some cancers. Accordingly, recent advances have focused on the inhibition of these transporters as a novel therapeutic strategy in cancers. To screen for MCT inhibitors for clinical application, it is important to study MCT function and regulation, and the effect of compounds on them, using human-derived cells. In this review, we focus on the transport function, regulation, and biology of hMCT1 and hMCT4, and the effects of genetic variation in these transporters in humans.
人单羧酸转运蛋白 1（hMCT1）和 4（hMCT4）参与质子依赖的单羧酸转运，如 L-乳酸，在细胞代谢和 pH 调节中发挥重要作用。hMCT1 和 4 在许多癌症中过度表达，并且已经报道 hMCT1 中的多态性与一些癌症的预后相关。因此，最近的研究进展集中在抑制这些转运体作为癌症的一种新的治疗策略。为了筛选用于临床应用的 MCT 抑制剂，研究人源细胞中 MCT 的功能和调节以及化合物对它们的影响非常重要。在这篇综述中，我们重点介绍 hMCT1 和 hMCT4 的转运功能、调节和生物学，以及这些转运体在人类中的遗传变异的影响。
