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

doi:10.1016/j.isci.2023.108564

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. eCollection 2023 Dec 15.

Authors

Lore Hoes^{1

2

3}, Karin Voordeckers^{1

2}, Rüveyda Dok³, Bram Boeckx^{4

5}, Bart Steemans⁶, Diyavarshini Gopaul⁷, Philippe Pasero⁷, Sander K Govers⁶, Diether Lambrechts^{4

5}, Sandra Nuyts^{3

8}, Kevin J Verstrepen^{1

2}

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.

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.