Mechanotransduction tuned by intermediate filaments promotes DNA repair in stiff environments
- 1Institut de Cancerologie de l'Ouest
Abstract
High mammographic density increases breast cancer risk. Dense tissues are rich in fibrillar collagen, forming a rigid extracellular matrix around the epithelium. Although cancer initiation and progression are closely tied to DNA damage and to the DNA damage response, if and how tissue stiffness affects genome maintenance is not fully elucidated. We found that repair factor recruitment is more efficient, and that DNA breaks are repaired faster by cells on rigid substrates. Mechanistically, hemidesmosomal integrins, intermediate filaments, the LINC complex, and YAP are key mediators of this mechanogenomic response. Rigid tissue contexts favor survival of cells with DNA damage, which may lead to the accumulation of somatic mutations, as identified here with RNAseq analyses of normal breast tissue. Our findings provide new insights into how tissue rigidity influences cancer risk.
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BibTeX
@misc{dehours2026mechanotransduction,
title = {{Mechanotransduction tuned by intermediate filaments promotes DNA repair in stiff environments}},
author = {C. Dehours and M. Locatelli and C. Lepetit and A. Smelser and H. Lee and J. Holmes and Q. Song and M. Gabber and M. Bertho and S. Lelievre and K. Bonin and M. Guthold and P.-A. Vidi},
howpublished = {bioRxiv},
year = {2026},
month = oct,
doi = {10.64898/2026.10.30.763110},
url = {https://www.biorxiv.org/content/10.64898/2026.10.30.763110v1},
note = {CC BY-NC-ND},
}
RIS
TY - UNPB
TI - Mechanotransduction tuned by intermediate filaments promotes DNA repair in stiff environments
AU - C. Dehours
AU - M. Locatelli
AU - C. Lepetit
AU - A. Smelser
AU - H. Lee
AU - J. Holmes
AU - Q. Song
AU - M. Gabber
AU - M. Bertho
AU - S. Lelievre
AU - K. Bonin
AU - M. Guthold
AU - P.-A. Vidi
PY - 2026
DA - 2026/10/30
PB - bioRxiv
DO - 10.64898/2026.10.30.763110
UR - https://www.biorxiv.org/content/10.64898/2026.10.30.763110v1
AB - High mammographic density increases breast cancer risk. Dense tissues are rich in fibrillar collagen, forming a rigid extracellular matrix around the epithelium. Although cancer initiation and progression are closely tied to DNA damage and to the DNA damage response, if and how tissue stiffness affects genome maintenance is not fully elucidated. We found that repair factor recruitment is more efficient, and that DNA breaks are repaired faster by cells on rigid substrates. Mechanistically, hemidesmosomal integrins, intermediate filaments, the LINC complex, and YAP are key mediators of this mechanogenomic response. Rigid tissue contexts favor survival of cells with DNA damage, which may lead to the accumulation of somatic mutations, as identified here with RNAseq analyses of normal breast tissue. Our findings provide new insights into how tissue rigidity influences cancer risk.
ER -