Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy.
Aldo-Keto Reductase AKR1C1-AKR1C4: Functions, Regulation, and Intervention for Anti-cancer Therapy.
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醛酮还原酶 AKR1C1-AKR1C4：抗癌治疗的功能、调节和干预
DOI：
10.3389/fphar.2017.00119
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发表时间：
2017
影响因子：
5.6
通讯作者：
Yang B
中科院分区：
文献类型：
--
作者：
Zeng CM;Chang LL;Ying MD;Cao J;He QJ;Zhu H;Yang B
醛酮还原酶由AKR 1C 1-AKR 1C 4组成，这四种酶催化NADPH依赖性还原，并与生物合成、中间代谢和解毒有关。近年来的研究表明，这些家族成员的表达水平与肿瘤的恶性转化以及对肿瘤治疗的耐药性密切相关。从机制上讲，大多数研究都集中在AKR 1C亚型的催化依赖性功能上，例如它们在前列腺癌、乳腺癌和由于广泛的底物特异性而产生的耐药性中的无可挑剔的作用。然而，越来越多的线索表明，催化剂独立的功能也发挥了重要作用，在调节生物事件。本文综述了AKR 1Cs的催化依赖性和非催化依赖性作用，以及针对这些家族成员的小分子抑制剂。
Aldo–keto reductases comprise of AKR1C1–AKR1C4, four enzymes that catalyze NADPH dependent reductions and have been implicated in biosynthesis, intermediary metabolism, and detoxification. Recent studies have provided evidences of strong correlation between the expression levels of these family members and the malignant transformation as well as the resistance to cancer therapy. Mechanistically, most studies focus on the catalytic-dependent function of AKR1C isoforms, like their impeccable roles in prostate cancer, breast cancer, and drug resistance due to the broad substrates specificity. However, accumulating clues showed that catalytic-independent functions also played critical roles in regulating biological events. This review summarizes the catalytic-dependent and -independent roles of AKR1Cs, as well as the small molecule inhibitors targeting these family members.