ALDH1L1 和 ALDH1L2 叶酸调节酶在癌症中的作用。

ALDH1L1 and ALDH1L2 Folate Regulatory Enzymes in Cancer.

机构信息

Department of Nutrition, University of North Carolina, Chapel Hill, NC, USA.

UNC Nutrition Research Institute, Chapel Hill, NC, USA.

出版信息

Adv Exp Med Biol. 2018;1032:127-143. doi: 10.1007/978-3-319-98788-0_10.

DOI:10.1007/978-3-319-98788-0_10

PMID:30362096

Abstract

Epidemiological studies implicate excess ethanol ingestion as a risk factor for several cancers and support the concept of a synergistic effect of chronic alcohol consumption and folate deficiency on carcinogenesis. Alcohol consumption affects folate-related genes and enzymes including two major folate-metabolizing enzymes, ALDH1L1 and ALDH1L2. ALDH1L1 (cytosolic 10-formyltetrahydrofolate dehydrogenase) is a regulatory enzyme in folate metabolism that controls the overall flux of one-carbon groups in folate-dependent biosynthetic pathways. It is strongly and ubiquitously down-regulated in malignant tumors via promoter methylation, and recent studies underscored this enzyme as a candidate tumor suppressor and potential marker of aggressive cancers. A related enzyme, ALDH1L2, is the mitochondrial homolog of ALDH1L1 encoded by a separate gene. In contrast to its cytosolic counterpart, ALDH1L2 is expressed in malignant tumors and cancer cell lines and was implicated in metastasis regulation. This review discusses the link between folate and cancer, modifying effects of alcohol consumption on folate-associated carcinogenesis, and putative roles of ALDH1L1 and ALDH1L2 in this process.

摘要

流行病学研究表明，过量饮酒是多种癌症的危险因素，并支持慢性酒精摄入和叶酸缺乏协同致癌的概念。饮酒会影响与叶酸相关的基因和酶，包括两种主要的叶酸代谢酶，ALDH1L1 和 ALDH1L2。ALDH1L1（胞质 10-甲酰四氢叶酸脱氢酶）是叶酸代谢中的调节酶，控制叶酸依赖性生物合成途径中一碳基团的整体通量。它通过启动子甲基化在恶性肿瘤中强烈且普遍地下调，最近的研究强调了该酶作为候选肿瘤抑制因子和侵袭性癌症的潜在标志物。另一种相关的酶，ALDH1L2，是由独立基因编码的 ALDH1L1 的线粒体同源物。与胞质对应物相反，ALDH1L2 在恶性肿瘤和癌细胞系中表达，并与转移调节有关。本文综述了叶酸与癌症之间的联系，以及饮酒对与叶酸相关的致癌作用的修饰作用，以及 ALDH1L1 和 ALDH1L2 在这一过程中的可能作用。