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.
Highlights
Aldehyde dehydrogenases (ALDHs) are a group of nicotinamide-adenine dinucleotide phosphate–positive (NAD(P)+)-dependent enzymes that catalyze the oxidation of endogenous and exogenous aldehyde substrates to their corresponding carboxylic acids [1,2,3]
There is accumulating evidence, based on the Aldeflour assay and IHC with isotype-specific antibodies, that supports the role for ALDH1A1 in stem cells (SC) and cancer stem cells (CSC)
The modulation of ALDH1A1 might play a key role in the regulation of growth and differentiation of both normal and cancer cells, influencing some aspects of the cancer phenotype and prognosis
Summary
Aldehyde dehydrogenases (ALDHs) are a group of nicotinamide-adenine dinucleotide phosphate–positive (NAD(P)+)-dependent enzymes that catalyze the oxidation of endogenous and exogenous aldehyde substrates to their corresponding carboxylic acids [1,2,3]. ALDH1A1 plays a vital role as a marker of SCs and cancer stem cells (CSCs).
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