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Review
. 2016 Jan;33(1):97-113.
doi: 10.1007/s10585-015-9755-9. Epub 2015 Oct 7.

Aldehyde dehydrogenase as a marker and functional mediator of metastasis in solid tumors

Mauricio Rodriguez-Torres  1   2 , Alison L Allan  3   4   5   6   7
Affiliations
Review

Aldehyde dehydrogenase as a marker and functional mediator of metastasis in solid tumors

Mauricio Rodriguez-Torres et al. Clin Exp Metastasis. 2016 Jan.

Abstract

There is accumulating evidence indicating that aldehyde dehydrogenase (ALDH) activity selects for cancer cells with increased aggressiveness, capacity for sustained proliferation, and plasticity in primary tumors. However, emerging data also suggests an important mechanistic role for the ALDH family of isoenzymes in the metastatic activity of tumor cells. Recent studies indicate that ALDH correlates with either increased or decreased metastatic capacity in a cellular context-dependent manner. Importantly, it appears that different ALDH isoforms support increased metastatic capacity in different tumor types. This review assesses the potential of ALDH as biological marker and mechanistic mediator of metastasis in solid tumors. In many malignancies, most notably in breast cancer, ALDH activity and expression appears to be a promising marker and potential therapeutic target for treating metastasis in the clinical setting.

Keywords: Aldehyde dehydrogenase; Biomarker; Cancer stem cell; Metastasis; Solid tumors.

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Figures

Fig. 1
Fig. 1
Molecular mechanisms associated with ALDH in metastasis promotion. The molecular mechanisms underlying the increased tumorigenicity and metastatic capacity of ALDHhi cancer cells involve diverse co-expressed molecular factors and signaling pathways. For example, in breast, ovarian, and pancreatic cancer, ALDH1A1 transcription has been shown to be regulated after binding of C/EBPβ, β-catenin, or Smad-4 to the ALDH1A1 promoter sequences (a, b). In breast cancer cells, Notch-induced deacetylation of ALDH1A1 can result in increased CSC capabilities (c). Taken together, these pathways influence downstream functional behaviors such as stem cell-related decisions regarding proliferation and cell fate, epithelial-to-mesenchymal transition, retinoic acid synthesis, hypoxia, DNA damage response, cytokine and RTK signaling activation, and cell migration (d), all of which may contribute to the role of ALDHhi cancer cells in metastasis promotion
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