Aldehyde dehydrogenase 3A1 promotes multi-modality resistance and alters gene expression profile in human breast adenocarcinoma MCF-7 cells

Abstract

Northumbria University has developed Northumbria Research Link (NRL) to enable users to access the University's research output. Copyright © and moral rights for items on NRL are retained by the individual author(s) and/or other copyright owners. Single copies of full items can be reproduced, displayed or performed, and given to third parties in any format or medium for personal research or study, educational, or not-for-profit purposes without prior permission or charge, provided the authors, title and full bibliographic details are given, as well as a hyperlink and/or URL to the original metadata page. The content must not be changed in any way. Full items must not be sold commercially in any format or medium without formal permission of the copyright holder. The full policy is available online: http://nrl.northumbria.ac.uk/policies.html This document may differ from the final, published version of the research and has been made available online in accordance with publisher policies. To read and/or cite from the published version of the research, please visit the publisher's website (a subscription may be required.)

Inhibition of Wnt/beta-catenin signaling downregulates expression of aldehyde dehydrogenase isoform 3A1 (ALDH3A1) to reduce resistance against temozolomide in glioblastoma in vitro

“…The data reported in the present study is in concordance with observations in other solid tumors. In both preclinical and clinical studies it has been reported that high levels of ALDH3A1 promote chemoresistance towards various common anti-cancer drugs and could be correlated with poor clinical prognosis [ 15 , 22 – 26 ]. Moreover, reports on other tumors outside the central nervous system suggest a positive correlation of ALDH3A1 expression and β-catenin signaling levels [ 26 – 29 ].…”

“…In both preclinical and clinical studies it has been reported that high levels of ALDH3A1 promote chemoresistance towards various common anti-cancer drugs and could be correlated with poor clinical prognosis [ 15 , 22 – 26 ]. Moreover, reports on other tumors outside the central nervous system suggest a positive correlation of ALDH3A1 expression and β-catenin signaling levels [ 26 – 29 ]. In head and neck squamous cell carcinoma, activation of ALDH3A1 increases chemoresistance against cisplatin whereas combining cisplatin with an ALDH inhibitor results in more pronounced cell viability reduction than treatment with each compound alone [ 30 ].…”

ALDH3A1 Overexpression in Melanoma and Lung Tumors Drives Cancer Stem Cell Expansion, Impairing Immune Surveillance through Enhanced PD-L1 Output

“…Reportedly, ALDH3A1 plays an important role in stemness in several solid cancers [6][7][8][9]. We examined ALDH3A1's ability to induce stem-cell-like features in WM and HCC cells by evaluating tumorsphere formation under non adherent culture conditions, and the expression of stem-like markers ( Figure 2).…”

“…By increasing NADPH availability during aldehyde detoxification, these enzymes link energetics and metabolism to the redox status of the cells, which in turn uses oxidant signals through transcription factor systems, including nuclear factor-kB (NFkB), to integrate energy efficiency, the resistance of cells to injury, and tissue repair [4]. Some ALDHs, particularly ALDH1A1, ALDH1A3, and ALDH3A1, are widely regarded as markers of stemness in normal tissues (basal skin, bronchial mucosa cells, human cornea, breast, liver), as well as in several solid tumors (non-small-cell lung cancer (NSCLC), melanoma, gastric, breast) [5][6][7][8][9]. However, recent evidence shows that these isozymes, rather than being a mere tag, are distinctly functional in the process of stem cell formation [10][11][12].…”

Engineered Animal Models Designed for Investigating Ethanol Metabolism, Toxicity and Cancer

“…The highest expression of Aldh3a1 occurs in the cornea, stomach, colon, urinary bladder, and skin of the mouse [86]. Numerous studies suggest a role for ALDH3A1 in a variety of homeostatic mechanisms, including cell proliferation, differentiation and apoptosis, and in resistance to chemotherapeutics used to treat human breast, hepatocellular or prostate adenocarcinoma [87–89]. ALDH3A1 appears to mediate these effects through both enzymatic and non-enzymatic properties.…”