Exploring the Role and Pathophysiological Significance of Aldehyde Dehydrogenase 1B1 (ALDH1B1) in Human Lung Adenocarcinoma

Aldehyde dehydrogenases (ALDHs) constitute a diverse superfamily of NAD(P) -dependent enzymes pivotal in oxidizing endogenous and exogenous aldehydes to carboxylic acids. Beyond metabolic roles, ALDHs participate in essential biological processes, including differentiation, embryogenesis and the DNA...

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Published in:	International journal of molecular sciences Vol. 25; no. 19; p. 10301
Main Authors:	Tsochantaridis, Ilias, Brisimis, Dimitris, Tsifintaris, Margaritis, Anastasiadou, Anastasia, Lazos, Efthymios, Ermogenous, Antreas, Christou, Sylia, Antonopoulou, Nefeli, Panayiotidis, Mihalis I, Koukourakis, Michail I, Giatromanolaki, Alexandra, Pappa, Aglaia
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 01-10-2024 MDPI
Subjects:	A549 A549 Cells Adenocarcinoma of Lung - genetics Adenocarcinoma of Lung - metabolism Adenocarcinoma of Lung - pathology Aldehyde Dehydrogenase 1 Family - genetics Aldehyde Dehydrogenase 1 Family - metabolism Aldehyde Dehydrogenase, Mitochondrial aldehyde dehydrogenases (ALDHs) ALDH1B1 Biomarkers Cancer Cell adhesion & migration Cell growth Cell Line, Tumor cell morphology Cell Movement Cell Proliferation chemoresistance Dehydrogenases Development and progression Drug Resistance, Neoplasm - genetics Efficiency Enzymes Epithelial-Mesenchymal Transition - genetics Flow cytometry Gene expression Gene Expression Regulation, Neoplastic Genotype & phenotype Health aspects Humans Lung cancer, Non-small cell Lung Neoplasms - genetics Lung Neoplasms - metabolism Lung Neoplasms - pathology Metastasis Morphology Neoplastic Stem Cells - metabolism Neoplastic Stem Cells - pathology Oxidoreductases Physiological aspects Signal Transduction Stem cells Greece CSC-related pathways chemoresistance ALDH1B1 cell proliferation A549 lung adenocarcinoma cancer stem cells (CSCs) migration cell morphology EMT aldehyde dehydrogenases (ALDHs)
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Summary:	Aldehyde dehydrogenases (ALDHs) constitute a diverse superfamily of NAD(P) -dependent enzymes pivotal in oxidizing endogenous and exogenous aldehydes to carboxylic acids. Beyond metabolic roles, ALDHs participate in essential biological processes, including differentiation, embryogenesis and the DNA damage response, while also serving as markers for cancer stem cells (CSCs). Aldehyde dehydrogenase 1B1 (ALDH1B1) is a mitochondrial enzyme involved in the detoxification of lipid peroxidation by-products and metabolism of various aldehyde substrates. This study examines the potential role of ALDH1B1 in human lung adenocarcinoma and its association with the CSC phenotype. To this end, we utilized the lung adenocarcinoma cell line A549, engineered to stably express the human ALDH1B1 protein tagged with green fluorescent protein (GFP). Overexpression of ALDH1B1 led to notable changes in cell morphology, proliferation rate and clonogenic efficiency. Furthermore, ALDH1B1-overexpressing A549 cells exhibited enhanced resistance to the chemotherapeutic agents etoposide and cisplatin. Additionally, ALDH1B1 overexpression correlated with increased migratory potential and epithelial-mesenchymal transition (EMT), mediated by the upregulation of transcription factors such as , and , alongside the downregulation of . Moreover, Spearman's rank correlation coefficient analysis using data from 507 publicly available lung adenocarcinoma clinical samples revealed a significant correlation between and various molecules implicated in CSC-related signaling pathways, including Wnt, Notch, hypoxia, Hedgehog, retinoic acid, Hippo, NF-κΒ, TGF-β, PI3K/PTEN-AKT and glycolysis/gluconeogenesis. These findings provide insights into the role of ALDH1B1 in lung tumor progression and its relation to the lung CSC phenotype, thereby offering potential therapeutic targets in the clinical management of lung adenocarcinoma.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms251910301