PDF(Pubmed)
Abstract：
Aldehyde dehydrogenases of the subfamily 1A (ALDH1A) are enzymes necessary for the oxidation of all-trans or 9-cis retinal to retinoic acid (RA). Retinoic acid and its derivatives are important for normal development and maintenance of epithelia, reproduction, memory, and immune function in adults. Moreover, in recent years, it has been demonstrated that ALDH1A members are also expressed and functional in several human cancers where their role is not limited to the synthesis of RA. Here, we review the current knowledge about ALDH1A3, one of the 1A isoforms, in cancers with an emphasis on two of the deadliest tumors that affect humans: glioblastoma multiforme and mesothelioma. In both tumors, ALDH1A3 is considered a negative prognostic factor, and its level correlates with excessive proliferation, chemoresistance, and invasiveness. We also review the recent attempts to develop both ALDH1A3-selective inhibitors for cancer therapy and ALDH1A3-specific fluorescent substrates for fluorescence-guided tumor resection.
摘要：
亚家族1A（ALDH1A）的醛脱氢酶是将全反式或9-顺式视黄醛氧化为视黄酸（RA）所必需的酶。视黄酸及其衍生物对上皮的正常发育和维持具有重要意义。繁殖，记忆,和成人的免疫功能。此外，近年来,已经证明ALDH1A成员也在几种人类癌症中表达和起作用,其中它们的作用不限于RA的合成。这里,我们回顾了关于ALDH1A3的最新知识，ALDH1A3是1A亚型之一，在癌症中，重点是影响人类的两种最致命的肿瘤：多形性胶质母细胞瘤和间皮瘤。在这两种肿瘤中，ALDH1A3被认为是一个负面的预后因素，它的水平与过度扩散相关，化学抗性，和侵入性。我们还回顾了最近开发用于癌症治疗的ALDH1A3选择性抑制剂和用于荧光引导肿瘤切除的ALDH1A3特异性荧光底物的尝试。
