title: Aldehyde dehydrogenase 1A1 in stem cells and cancer.
abstract: 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.
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Tomita
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.|Department of Surgical Oncology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Kaori
authors.initials: K
authors.lastname: Tanaka
authors.affiliation: Division of Pathology, Gifu Municipal Hospital, Gifu, Japan.
authors.forename: Takuji
authors.initials: T
authors.lastname: Tanaka
authors.affiliation: Department of Tumor Pathology, Gifu University Graduate School of Medicine, Gifu, Japan.
authors.forename: Akira
authors.initials: A
authors.lastname: Hara
mesh_terms: D000444:Aldehyde Dehydrogenase / Q000378:metabolism*; D000080924:Aldehyde Dehydrogenase 1 Family; D000818:Animals; D006801:Humans; D009369:Neoplasms / Q000201:enzymology* / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000201:enzymology* / Q000473:pathology*; D050697:Retinal Dehydrogenase
chemical_list: D000080924:Aldehyde Dehydrogenase 1 Family; D000444:Aldehyde Dehydrogenase; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: ALDH; ALDH1A1; aldehyde dehydrogenase; cancer; stem cell