Files and links (1)
Published, Version of Record (VoR)CC BY V4.0, Open
Journal article
Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy
Biomolecules (Basel, Switzerland), v 11(10), p1479
01 Oct 2021
PMID: 34680112
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Background: Alcohol (ethanol) consumption is a major risk factor for head and neck and esophageal squamous cell carcinomas (SCCs). However, how ethanol (EtOH) affects SCC homeostasis is incompletely understood. Methods: We utilized three-dimensional (3D) organoids and xenograft tumor transplantation models to investigate how EtOH exposure influences intratumoral SCC cell populations including putative cancer stem cells defined by high CD44 expression (CD44H cells). Results: Using 3D organoids generated from SCC cell lines, patient-derived xenograft tumors, and patient biopsies, we found that EtOH is metabolized via alcohol dehydrogenases to induce oxidative stress associated with mitochondrial superoxide generation and mitochondrial depolarization, resulting in apoptosis of the majority of SCC cells within organoids. However, CD44H cells underwent autophagy to negate EtOH-induced mitochondrial dysfunction and apoptosis and were subsequently enriched in organoids and xenograft tumors when exposed to EtOH. Importantly, inhibition of autophagy increased EtOH-mediated apoptosis and reduced CD44H cell enrichment, xenograft tumor growth, and organoid formation rate. Conclusions: This study provides mechanistic insights into how EtOH may influence SCC cells and establishes autophagy as a potential therapeutic target for the treatment of EtOH-associated SCC.
Metrics
Details
- Title
- Alcohol Metabolism Enriches Squamous Cell Carcinoma Cancer Stem Cells That Survive Oxidative Stress via Autophagy
- Creators
- Masataka Shimonosono - Columbia UniversityKoji Tanaka - Osaka UniversitySamuel Flashner - Columbia UniversitySatoshi Takada - Columbia UniversityNorihiro Matsuura - Columbia UniversityYasuto Tomita - Columbia UniversityUma M. Sachdeva - Columbia UniversityEishi Noguchi - Drexel UniversityVeena Sangwan - Montreal General HospitalLorenzo Ferri - Montreal General HospitalFatemeh Momen-Heravi - Columbia UniversityAngela J. Yoon - Columbia UniversityAndres J. Klein-Szanto - Fox Chase Cancer CenterJ. Alan Diehl - Case Western Reserve UniversityHiroshi Nakagawa - Columbia University
- Publication Details
- Biomolecules (Basel, Switzerland), v 11(10), p1479
- Publisher
- Mdpi
- Number of pages
- 19
- Grant note
- C0608 / W. W. Smith Charitable Trust Thoracic Surgery Foundation/Women in Thoracic Surgery P01CA098101; U54CA163004; R01DK114436; R01DE026801; R01AA026297; L30CA264714; P30CA013696 / NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA Columbia University Herbert Irving Comprehensive Cancer Center Multi-PI Pilot Award Eleanor and Miles Shore Fellowship from Harvard Medical School/MGH
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Biochemistry and Molecular Biology
- Web of Science ID
- WOS:000747218200001
- Scopus ID
- 2-s2.0-85116408489
- Other Identifier
- 991019168229504721
UN Sustainable Development Goals (SDGs)
This publication has contributed to the advancement of the following goals:
InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Collaboration types
- Domestic collaboration
- International collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology