Ethanol induces replication fork stalling and membrane stress in immortalized laryngeal cells
Lore Hoes,
Karin Voordeckers,
Rüveyda Dok,
Bram Boeckx,
Bart Steemans,
Diyavarshini Gopaul,
Philippe Pasero,
Sander K. Govers,
Diether Lambrechts,
Sandra Nuyts,
Kevin J. Verstrepen
Affiliations
Lore Hoes
Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, 3000 Leuven; Laboratory of Genetics and Genomics, Centre for Microbial and Plant Genetics, KU Leuven, 3000 Leuven, Belgium; Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, 3000 Leuven, Belgium; Corresponding author
Karin Voordeckers
Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, 3000 Leuven; Laboratory of Genetics and Genomics, Centre for Microbial and Plant Genetics, KU Leuven, 3000 Leuven, Belgium
Rüveyda Dok
Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, 3000 Leuven, Belgium
Bram Boeckx
Laboratory of Translational Genetics, VIB-KU Leuven Center for Cancer Biology, 3000 Leuven, Belgium; Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium
Bart Steemans
Laboratory of Microbial Systems Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, Belgium
Diyavarshini Gopaul
Institute of Human Genetics, CNRS, University of Montpellier, 34396 Montpellier, France
Philippe Pasero
Institute of Human Genetics, CNRS, University of Montpellier, 34396 Montpellier, France
Sander K. Govers
Laboratory of Microbial Systems Cell Biology, Department of Biology, KU Leuven, 3000 Leuven, Belgium
Diether Lambrechts
Laboratory of Translational Genetics, VIB-KU Leuven Center for Cancer Biology, 3000 Leuven, Belgium; Laboratory of Translational Genetics, Department of Human Genetics, KU Leuven, 3000 Leuven, Belgium
Sandra Nuyts
Laboratory of Experimental Radiotherapy, Department of Oncology, KU Leuven, 3000 Leuven, Belgium; Department of Radiation Oncology, Leuven Cancer Institute, University Hospital Leuven, 3000 Leuven, Belgium
Kevin J. Verstrepen
Laboratory for Systems Biology, VIB-KU Leuven Center for Microbiology, 3000 Leuven; Laboratory of Genetics and Genomics, Centre for Microbial and Plant Genetics, KU Leuven, 3000 Leuven, Belgium
Summary: 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.
