Vimentin loss inhibits DNA damage responses and promotes cancer cell survival
Abstract
Vimentin intermediate filaments are a hallmark of aggressive tumours and are widely linked to invasion and EMT, yet how vimentin-dependent mechanics shape genome maintenance and therapy response is unclear. Here we show that vimentin, particularly under compressive load, promotes DNA repair competence. In contrast, vimentin-negative cells show impaired DNA damage sensing and downstream signaling, ultimately leading to decreased apoptosis and promoting cell survival under genotoxic stress at the expense of genomic stability. Using controlled cell compression together with genetic and pharmacological perturbations, we find that loss of vimentin in glioblastoma cells limits the expression and activity of core repair pathways because of induced nuclear mechanical compression. Relieving nuclear compression restores DNA damage accumulation and repair kinetics. Functionally, suppression of DNA damage responses enhances survival after clinically relevant DNA-damaging treatments, including temozolomide, X-Ray radiation and cell invasion through tight spaces. These findings invert the prevailing view that vimentin's contribution to tumour progression stems from enhanced migration and identify a mechanochemical vimentin-nucleus axis that tunes DNA damage responses to favor therapy tolerance and genome evolution.
Related
- Eriocitrin promotes apoptosis and inhibits invasion and proliferation of androgen-independent prostate cancer via the PI3K/AKT/mTOR pathway
- Licochalcone A Inhibits Melanoma Cell Survival by Suppressing HSP75 (TRAP1) and Disrupting Cellular Redox and Energy Homeostasis
- Microscale spatial fragmentation promotes bacterial survival under antibiotics
- A case for DNA-membrane interactions in the responses to DNA damage
- Glutamine synthesis pathway promotes the survival and recurrence of dormant tumor cells in prostate cancer.
BibTeX
@article{infante2026vimentin,
title = {{Vimentin loss inhibits DNA damage responses and promotes cancer cell survival}},
author = {Elvira Infante and Emmanuel Terriac and Matthieu Gelin and Vanessa Roca and Saline Jabre and Hugo Siegfried and David Pereira and Hugo Varet and Sara Khalilian and Atef Asnacios and Emma J van Bodegraven and Sandrine Etienne-Manneville},
journal = {EMBO Reports},
year = {2026},
month = sep,
doi = {10.1038/s44319-026-00913-2},
url = {https://pasteur.hal.science/pasteur-05740254v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Vimentin loss inhibits DNA damage responses and promotes cancer cell survival
AU - Elvira Infante
AU - Emmanuel Terriac
AU - Matthieu Gelin
AU - Vanessa Roca
AU - Saline Jabre
AU - Hugo Siegfried
AU - David Pereira
AU - Hugo Varet
AU - Sara Khalilian
AU - Atef Asnacios
AU - Emma J van Bodegraven
AU - Sandrine Etienne-Manneville
PY - 2026
DA - 2026/09/04
JO - EMBO Reports
DO - 10.1038/s44319-026-00913-2
UR - https://pasteur.hal.science/pasteur-05740254v1
AB - Vimentin intermediate filaments are a hallmark of aggressive tumours and are widely linked to invasion and EMT, yet how vimentin-dependent mechanics shape genome maintenance and therapy response is unclear. Here we show that vimentin, particularly under compressive load, promotes DNA repair competence. In contrast, vimentin-negative cells show impaired DNA damage sensing and downstream signaling, ultimately leading to decreased apoptosis and promoting cell survival under genotoxic stress at the expense of genomic stability. Using controlled cell compression together with genetic and pharmacological perturbations, we find that loss of vimentin in glioblastoma cells limits the expression and activity of core repair pathways because of induced nuclear mechanical compression. Relieving nuclear compression restores DNA damage accumulation and repair kinetics. Functionally, suppression of DNA damage responses enhances survival after clinically relevant DNA-damaging treatments, including temozolomide, X-Ray radiation and cell invasion through tight spaces. These findings invert the prevailing view that vimentin's contribution to tumour progression stems from enhanced migration and identify a mechanochemical vimentin-nucleus axis that tunes DNA damage responses to favor therapy tolerance and genome evolution.
SN - 1469-221X
SN - 1469-3178
ER -