The role of ABCC10/MRP7 in anti-cancer drug resistance and beyond

IF 15.8 1区医学 Q1 PHARMACOLOGY & PHARMACY

Drug Resistance Updates Pub Date : 2024-01-29 DOI:10.1016/j.drup.2024.101062

Da-Qian Chen , Yuhao Xie , Lu-Qi Cao , Joshua S. Fleishman , Yang Chen , Tiesong Wu , Dong-Hua Yang

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Abstract

Multidrug resistance protein 7 (MRP7), also known as ATP-binding cassette (ABC) transporter subfamily C10 (ABCC10), is an ABC transporter that was first identified in 2001. ABCC10/MRP7 is a 171 kDa protein located on the basolateral membrane of cells. ABCC10/MRP7 consists of three transmembrane domains and two nucleotide binding domains. It mediates multidrug resistance of tumor cells to a variety of anticancer drugs by increasing drug efflux and results in reducing intracellular drug accumulation. The transport substrates of ABCC10/MRP7 include antineoplastic drugs such as taxanes, vinca alkaloids, and epothilone B, as well as endobiotics such as leukotriene C4 (LTC₄) and estradiol 17 β-D-glucuronide. A variety of ABCC10/MRP7 inhibitors, including cepharanthine, imatinib, erlotinib, tariquidar, and sildenafil, can reverse ABCC10/MRP7-mediated MDR. Additionally, the presence or absence of ABCC10/MRP7 is also closely related to renal tubular dysfunction, obesity, and other diseases. In this review, we discuss: 1) Structure and functions of ABCC10/MRP7; 2) Known substrates and inhibitors of ABCC10/MRP7 and their potential therapeutic applications in cancer; and 3) Role of ABCC10/MRP7 in non-cancerous diseases.

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ABCC10 / MRP7 在抗癌药物耐药性及其他方面的作用

多药耐药性蛋白 7（MRP7）又称 ATP 结合盒（ABC）转运体 C10 亚家族（ABCC10），是一种 ABC 转运体，于 2001 年首次被发现。ABCC10/MRP7 是一种 171 kDa 的蛋白质，位于细胞的基底侧膜上。ABCC10/MRP7 由三个跨膜结构域和两个核苷酸结合结构域组成。它通过增加药物外流来介导肿瘤细胞对多种抗癌药物的多药耐药性，从而减少细胞内的药物积累。ABCC10/MRP7 的转运底物包括紫杉类、长春花生物碱和埃博霉素 B 等抗肿瘤药物，以及白三烯 C4（LTC4）和雌二醇 17 β-D-葡萄糖醛酸苷等内生药物。多种 ABCC10/MRP7 抑制剂，包括西酞普兰、伊马替尼、厄洛替尼、他利奎达和西地那非，都能逆转 ABCC10/MRP7 介导的 MDR。此外，ABCC10/MRP7的存在与否还与肾小管功能障碍、肥胖和其他疾病密切相关。在本综述中，我们将讨论1）ABCC10/MRP7 的结构和功能；2）ABCC10/MRP7 的已知底物和抑制剂及其在癌症中的潜在治疗应用；以及 3）ABCC10/MRP7 在非癌症疾病中的作用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Drug Resistance Updates 医学-药学

CiteScore

26.20

自引率

11.90%

发文量

审稿时长

29 days

期刊介绍： Drug Resistance Updates serves as a platform for publishing original research, commentary, and expert reviews on significant advancements in drug resistance related to infectious diseases and cancer. It encompasses diverse disciplines such as molecular biology, biochemistry, cell biology, pharmacology, microbiology, preclinical therapeutics, oncology, and clinical medicine. The journal addresses both basic research and clinical aspects of drug resistance, providing insights into novel drugs and strategies to overcome resistance. Original research articles are welcomed, and review articles are authored by leaders in the field by invitation. Articles are written by leaders in the field, in response to an invitation from the Editors, and are peer-reviewed prior to publication. Articles are clear, readable, and up-to-date, suitable for a multidisciplinary readership and include schematic diagrams and other illustrations conveying the major points of the article. The goal is to highlight recent areas of growth and put them in perspective. *Expert reviews in clinical and basic drug resistance research in oncology and infectious disease *Describes emerging technologies and therapies, particularly those that overcome drug resistance *Emphasises common themes in microbial and cancer research