The Expanding Role of Cancer Stem Cell Marker ALDH1A3 in Cancer and Beyond

Meghan E. McLean; Maya R. MacLean; Hannah F. Cahill; Raj Pranap Arun; Olivia L. Walker; Marie Claire D. Wasson; Wasundara Fernando; Jaganathan Venkatesh; Paola Marcato

doi:10.3390/cancers15020492

The Expanding Role of Cancer Stem Cell Marker ALDH1A3 in Cancer and Beyond

Meghan E. McLean, Maya R. MacLean, Hannah F. Cahill, Raj Pranap Arun, Olivia L. Walker, Marie Claire D. Wasson, Wasundara Fernando, Jaganathan Venkatesh, Paola Marcato

Research output: Contribution to journal › Review article › peer-review

25 Citations (Scopus)

Abstract

Aldehyde dehydrogenase 1A3 (ALDH1A3) is one of 19 ALDH enzymes expressed in humans, and it is critical in the production of hormone receptor ligand retinoic acid (RA). We review the role of ALDH1A3 in normal physiology, its identification as a cancer stem cell marker, and its modes of action in cancer and other diseases. ALDH1A3 is often over-expressed in cancer and promotes tumor growth, metastasis, and chemoresistance by altering gene expression, cell signaling pathways, and glycometabolism. The increased levels of ALDH1A3 in cancer occur due to genetic amplification, epigenetic modifications, post-transcriptional regulation, and post-translational modification. Finally, we review the potential of targeting ALDH1A3, with both general ALDH inhibitors and small molecules specifically designed to inhibit ALDH1A3 activity.

Original language	English
Article number	492
Journal	Cancers
Volume	15
Issue number	2
DOIs	https://doi.org/10.3390/cancers15020492
Publication status	Published - Jan 2023

Bibliographical note

Funding Information:
M.E.M. is funded by a Faculty of Medicine Scholarship and a Nova Scotia Graduate Scholarship. H.F.C. is funded by a Research Nova Scotia Masters Scotia Scholar studentship and a Nova Scotia Graduate Scholarship. O.L.W. is funded by a Killam Predoctoral Scholarship and the President’s Award. M.-C.D.W. is funded by the Research Nova Scotia Scholar Award, a Nova Scotia Graduate Studentship and is supported by the Cancer Research Training Program (CRTP) from the Beatrice Hunter Cancer Research Institute (BHCRI). R.P.A. is a trainee in the CRTP of the BHRCRI, with funds generously provided by the Canadian Cancer Society’s JD Irving, Limited—Excellence in Cancer Research Fund. W.F. is funded by a Dalhousie Medical Research Foundation-I3V Dr. David H. Hubel Postdoctoral Fellowship. J.V. is a trainee in the CRTP of the BHRCRI, with funds generously provided by GIVETOLIVE. The article was funded by grant support to P.M. from the Canadian Institutes of Health Research (CHIR, PJT 162313).

Publisher Copyright:
© 2023 by the authors.

ASJC Scopus Subject Areas

Oncology
Cancer Research

PubMed: MeSH publication types

Journal Article
Review

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.3390/cancers15020492

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title = "The Expanding Role of Cancer Stem Cell Marker ALDH1A3 in Cancer and Beyond",

abstract = "Aldehyde dehydrogenase 1A3 (ALDH1A3) is one of 19 ALDH enzymes expressed in humans, and it is critical in the production of hormone receptor ligand retinoic acid (RA). We review the role of ALDH1A3 in normal physiology, its identification as a cancer stem cell marker, and its modes of action in cancer and other diseases. ALDH1A3 is often over-expressed in cancer and promotes tumor growth, metastasis, and chemoresistance by altering gene expression, cell signaling pathways, and glycometabolism. The increased levels of ALDH1A3 in cancer occur due to genetic amplification, epigenetic modifications, post-transcriptional regulation, and post-translational modification. Finally, we review the potential of targeting ALDH1A3, with both general ALDH inhibitors and small molecules specifically designed to inhibit ALDH1A3 activity.",

author = "McLean, {Meghan E.} and MacLean, {Maya R.} and Cahill, {Hannah F.} and Arun, {Raj Pranap} and Walker, {Olivia L.} and Wasson, {Marie Claire D.} and Wasundara Fernando and Jaganathan Venkatesh and Paola Marcato",

note = "Funding Information: M.E.M. is funded by a Faculty of Medicine Scholarship and a Nova Scotia Graduate Scholarship. H.F.C. is funded by a Research Nova Scotia Masters Scotia Scholar studentship and a Nova Scotia Graduate Scholarship. O.L.W. is funded by a Killam Predoctoral Scholarship and the President{\textquoteright}s Award. M.-C.D.W. is funded by the Research Nova Scotia Scholar Award, a Nova Scotia Graduate Studentship and is supported by the Cancer Research Training Program (CRTP) from the Beatrice Hunter Cancer Research Institute (BHCRI). R.P.A. is a trainee in the CRTP of the BHRCRI, with funds generously provided by the Canadian Cancer Society{\textquoteright}s JD Irving, Limited—Excellence in Cancer Research Fund. W.F. is funded by a Dalhousie Medical Research Foundation-I3V Dr. David H. Hubel Postdoctoral Fellowship. J.V. is a trainee in the CRTP of the BHRCRI, with funds generously provided by GIVETOLIVE. The article was funded by grant support to P.M. from the Canadian Institutes of Health Research (CHIR, PJT 162313). Publisher Copyright: {\textcopyright} 2023 by the authors.",

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N2 - Aldehyde dehydrogenase 1A3 (ALDH1A3) is one of 19 ALDH enzymes expressed in humans, and it is critical in the production of hormone receptor ligand retinoic acid (RA). We review the role of ALDH1A3 in normal physiology, its identification as a cancer stem cell marker, and its modes of action in cancer and other diseases. ALDH1A3 is often over-expressed in cancer and promotes tumor growth, metastasis, and chemoresistance by altering gene expression, cell signaling pathways, and glycometabolism. The increased levels of ALDH1A3 in cancer occur due to genetic amplification, epigenetic modifications, post-transcriptional regulation, and post-translational modification. Finally, we review the potential of targeting ALDH1A3, with both general ALDH inhibitors and small molecules specifically designed to inhibit ALDH1A3 activity.

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The Expanding Role of Cancer Stem Cell Marker ALDH1A3 in Cancer and Beyond

Abstract

Bibliographical note

ASJC Scopus Subject Areas

PubMed: MeSH publication types

UN SDGs

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