Aldehyde dehydrogenase 1A1 in stem cells and cancer.
Aldehyde dehydrogenase 1A1 in stem cells and cancer.
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DOI：
10.18632/oncotarget.6920
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发表时间：
2016-03-08
期刊：
影响因子：
--
通讯作者：
Hara A
中科院分区：
文献类型：
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作者：
Tomita H;Tanaka K;Tanaka T;Hara A
人类基因组包含19个假定有功能的醛脱氢酶（ALDH）基因，这些基因编码的酶通过依赖NAD（P）⁺的氧化作用对内源和外源醛底物的解毒至关重要。ALDH1有三种主要的亚型，即ALDH1A1、ALDH1A2和ALDH1A3，它是正常组织干细胞（SC）和癌症干细胞（CSC）的标志物，在其中参与自我更新、分化和自我保护。对小鼠和人类细胞的实验表明，主要归因于ALDH1A1亚型的ALDH1活性具有组织和癌症特异性。高ALDH1活性和ALDH1A1过表达与癌症预后不良有关，尽管高ALDH1和ALDH1A1水平并不总是与高度恶性的表型和不良的临床结果相关。在癌症治疗中，ALDH1A1在正常情况下不表达高水平ALDH1A1的组织类型（包括乳腺、肺、食管、结肠和胃）中提供了一个有用的癌症干细胞治疗靶点。在此我们综述了ALDH1A1的功能和机制，它是与干细胞群体相关的关键ALDH同工酶，也是癌症中癌症干细胞功能的重要贡献者，并且我们概述了它在未来抗癌策略中的潜力。
The human genome contains 19 putatively functional aldehyde dehydrogenase (ALDH) genes, which encode enzymes critical for detoxification of endogenous and exogenous aldehyde substrates through NAD(P)+-dependent oxidation. ALDH1 has three main isotypes, ALDH1A1, ALDH1A2, and ALDH1A3, and is a marker of normal tissue stem cells (SC) and cancer stem cells (CSC), where it is involved in self-renewal, differentiation and self-protection. Experiments with murine and human cells indicate that ALDH1 activity, predominantly attributed to isotype ALDH1A1, is tissue- and cancer-specific. High ALDH1 activity and ALDH1A1 overexpression are associated with poor cancer prognosis, though high ALDH1 and ALDH1A1 levels do not always correlate with highly malignant phenotypes and poor clinical outcome. In cancer therapy, ALDH1A1 provides a useful therapeutic CSC target in tissue types that normally do not express high levels of ALDH1A1, including breast, lung, esophagus, colon and stomach. Here we review the functions and mechanisms of ALDH1A1, the key ALDH isozyme linked to SC populations and an important contributor to CSC function in cancers, and we outline its potential in future anticancer strategies.