2. Academic Validation
  3. Ethanol induces replication fork stalling and membrane stress in immortalized laryngeal cells

Ethanol induces replication fork stalling and membrane stress in immortalized laryngeal cells

  • iScience. 2023 Nov 23;26(12):108564. doi: 10.1016/j.isci.2023.108564.
Lore Hoes 1 2 3,  Karin Voordeckers 1 2,  Rüveyda Dok 3,  Bram Boeckx 4 5,  Bart Steemans 6,  Diyavarshini Gopaul 7,  Philippe Pasero 7,  Sander K Govers 6,  Diether Lambrechts 4 5,  Sandra Nuyts 3 8,  Kevin J Verstrepen 1 2
Affiliations

Affiliations

  • 1 Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, 3000 Leuven.
  • 2 Laboratory of Genetics and Genomics, Centre for Microbial and Plant Genetics, KU Leuven, 3000 Leuven, Belgium.
  • 3 Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, 3000 Leuven, Belgium.
  • 4 Laboratory of Translational Genetics, VIB-KU Leuven Center for Cancer Biology, 3000 Leuven, Belgium.
  • 5 Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium.
  • 6 Laboratory of Microbial Systems Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, Belgium.
  • 7 Institute of Human Genetics, CNRS, University of Montpellier, 34396 Montpellier, France.
  • 8 Department of Radiation Oncology, Leuven Cancer Institute, University Hospital Leuven, 3000 Leuven, Belgium.
PMID: 38213791 DOI: 10.1016/j.isci.2023.108564
Abstract

Although ethanol is a class I carcinogen and is linked to more than 700,000 Cancer incidences, a clear understanding of the molecular mechanisms underlying ethanol-related carcinogenesis is still lacking. Further understanding of ethanol-related cell damage can contribute to reducing or treating alcohol-related cancers. Here, we investigated the effects of both short- and long-term exposure of human laryngeal epithelial cells to different ethanol concentrations. RNA Sequencing shows that ethanol altered gene expression patterns in a time- and concentration-dependent way, affecting genes involved in ribosome biogenesis, Cytoskeleton remodeling, Wnt signaling, and transmembrane ion transport. Additionally, ethanol induced a slower cell proliferation, a delayed cell cycle progression, and replication fork stalling. In addition, ethanol exposure resulted in morphological changes, which could be associated with membrane stress. Taken together, our data yields a comprehensive view of molecular changes associated with ethanol stress in epithelial cells of the upper aerodigestive tract.

Keywords

Cancer; Omics.

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