ArticleAmerican journal of cancer research2016
ALDH2 modulates autophagy flux to regulate acetaldehyde-mediated toxicity thresholds.
Article in American journal of cancer research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
What it found
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Who cites it
20 citing papers in PubMed, 28 citations in OpenAlex.
- The Role of Mitochondrial DNA in Modulating Chemoresistance in Esophageal Cancer: Mechanistic Insights and Therapeutic Potential.Biomolecules · 2025Review
- Deciphering the dual role of autophagy in gastric cancer and gastroesophageal junction cancer: from tumor suppression to cancer progression.Discover oncology · 2025Review
- Aldh2 and the tumor suppressor Trp53 play important roles in alcohol-induced squamous field cancerization.Journal of gastroenterology · 2025Article
- [Research progress of aldehyde dehydrogenase type 2 in head and neck malignant tumors].Lin chuang er bi yan hou tou jing wai ke za zhi = Journal of clinical otorhinolaryngology head and neck surgery · 2025Review
- ALDH2 dysfunction and alcohol cooperate in cancer stem cell enrichment.Carcinogenesis · 2024Article
- The p53 DNA damage response and Fanconi anemia DNA repair pathway protect against acetaldehyde-induced replication stress in esophageal keratinocytes.Cell cycle (Georgetown, Tex.) · 2023Article
- The applications and techniques of organoids in head and neck cancer therapy.Frontiers in oncology · 2023Review
- FANCD2 limits acetaldehyde-induced genomic instability during DNA replication in esophageal keratinocytes.Molecular oncology · 2021Article
- Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy.Biomolecules · 2021Article
- The role of ALDH2 in tumorigenesis and tumor progression: Targeting ALDH2 as a potential cancer treatment.Acta pharmaceutica Sinica. B · 2021Review
- Ethanol exposure increases mutation rate through error-prone polymerases.Nature communications · 2020Article
- Autophagy mitigates ethanol-induced mitochondrial dysfunction and oxidative stress in esophageal keratinocytes.PloS one · 2020Article
- Why is there selective subcortical vulnerability in ADHD? Clues from postmortem brain gene expression data.Molecular psychiatry · 2018Article
- ALDH2 protects against high fat diet-induced obesity cardiomyopathy and defective autophagy: role of CaM kinase II, histone H3K9 methyltransferase SUV39H, Sirt1, and PGC-1α deacetylation.International journal of obesity (2005) · 2018Article
- Esophageal 3D Culture Systems as Modeling Tools in Esophageal Epithelial Pathobiology and Personalized Medicine.Cellular and molecular gastroenterology and hepatology · 2018Review
- Interplay between Notch1 and Notch3 promotes EMT and tumor initiation in squamous cell carcinoma.Nature communications · 2017Article
- Gene-environment interactions involving functional variants: Results from the Breast Cancer Association Consortium.International journal of cancer · 2017Article
- Molecular Mechanisms of Acetaldehyde-Mediated Carcinogenesis in Squamous Epithelium.International journal of molecular sciences · 2017Review
- Article
- Mitochondrial dysfunction and mitochondrial dynamics-The cancer connection.Biochimica et biophysica acta. Bioenergetics · 2017Review
Corrections and comments
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Authors and funding
15 authors at 2 institutions in 2 countries.
Funding
Abstract
A polymorphic mutation in the acetaldehyde dehydrogenase 2 (ALDH2) gene has been epidemiologically linked to the high susceptibility to esophageal carcinogenesis for individuals with alcohol use disorders. Mice subjected to alcohol drinking show increased oxidative stress and DNA adduct formation in esophageal epithelia where Aldh2 loss augments alcohol-induced genotoxic effects; however, it remains elusive as to how esophageal epithelial cells with dysfunctional Aldh2 cope with oxidative stress related to alcohol metabolism. Here, we investigated the role of autophagy in murine esophageal epithelial cells (keratinocytes) exposed to ethanol and acetaldehyde. We find that ethanol and acetaldehyde trigger oxidative stress via mitochondrial superoxide in esophageal keratinocytes. Aldh2-deficient cells appeared to be highly susceptible to ethanol- or acetaldehyde-mediated toxicity. Alcohol dehydrogenase-mediated acetaldehyde production was implicated in ethanol-induced cell injury in Aldh2 deficient cells as ethanol-induced oxidative stress and cell death was partially inhibited by 4-methylpyrazole. Acetaldehyde activated autophagy flux in esophageal keratinocytes where Aldh2 deficiency increased dependence on autophagy to cope with ethanol-induced acetaldehyde-mediated oxidative stress. Pharmacological inhibition of autophagy flux by chloroquine stabilized p62/SQSTM1, and increased basal and acetaldehyde-mediate oxidative stress in Aldh2 deficient cells as documented in monolayer culture as well as single-cell derived three-dimensional esophageal organoids, recapitulating a physiological esophageal epithelial proliferation-differentiation gradient. Our innovative approach indicates, for the first time, that autophagy may provide cytoprotection to esophageal epithelial cells responding to oxidative stress that is induced by ethanol and its major metabolite acetaldehyde. Defining autophagymediated cytoprotection against alcohol-induced genotoxicity in the context of Aldh2 deficiency, our study provides mechanistic insights into the tumor suppressor functions of ALDH2 and autophagy in alcohol-related esophageal carcinogenesis.
Indexed as
Identifiers
27186430PMC4859883W2406470751What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.