Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress.
- 1Department of Cell Biology, University of Virginia School of Medicine, Charlottesville, VA, USA.
- 2Department of Radiology and Oncology, Rutgers Cancer Institute of New Jersey, New Brunswick, NJ, USA.
Abstract
Invasively migrating cells thread their nucleus through confined interstitial spaces. How cells protect the nucleus from intracellular forces is poorly understood. Here, we show that the septin cytoskeleton buffers the actomyosin forces that have been shown to power nuclear movement. Septin filaments comprising SEPT9, a septin amplified in breast cancer, align with perinuclear actomyosin cables, which exhibit higher tensile stress during 3D confined migration through narrower pores. SEPT9 depletion amplifies actin stress during confined migration and after myosin II hyperactivation in nonmigrating cells causing actin and nuclear envelope ruptures. Following confined migration, DNA breaks, nuclear blebs, micronuclei, and cell death increase in SEPT9-depleted cells, phenotypes rescued by the oncogenic SEPT9 isoform 1. Clinicogenomic data reveal that SEPT9 amplification associates with lower genomic alteration in aggressive breast tumors. We propose that septins are a mechanoprotective element of the cytoskeleton, and SEPT9 amplification enhances tumor cell survival by preventing nuclear damage.
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BibTeX
@article{pozo2026septins,
title = {{Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress.}},
author = {Franklin Mayca Pozo and Sarah M Butts and Andrew W Schaefer and Cristina Montagna and Elias T Spiliotis},
journal = {The Journal of cell biology},
year = {2026},
month = oct,
doi = {10.1083/jcb.202602074},
url = {https://europepmc.org/article/MED/42911177},
note = {CC BY},
}
RIS
TY - JOUR
TI - Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress.
AU - Franklin Mayca Pozo
AU - Sarah M Butts
AU - Andrew W Schaefer
AU - Cristina Montagna
AU - Elias T Spiliotis
PY - 2026
DA - 2026/10/22
JO - The Journal of cell biology
DO - 10.1083/jcb.202602074
UR - https://europepmc.org/article/MED/42911177
AB - Invasively migrating cells thread their nucleus through confined interstitial spaces. How cells protect the nucleus from intracellular forces is poorly understood. Here, we show that the septin cytoskeleton buffers the actomyosin forces that have been shown to power nuclear movement. Septin filaments comprising SEPT9, a septin amplified in breast cancer, align with perinuclear actomyosin cables, which exhibit higher tensile stress during 3D confined migration through narrower pores. SEPT9 depletion amplifies actin stress during confined migration and after myosin II hyperactivation in nonmigrating cells causing actin and nuclear envelope ruptures. Following confined migration, DNA breaks, nuclear blebs, micronuclei, and cell death increase in SEPT9-depleted cells, phenotypes rescued by the oncogenic SEPT9 isoform 1. Clinicogenomic data reveal that SEPT9 amplification associates with lower genomic alteration in aggressive breast tumors. We propose that septins are a mechanoprotective element of the cytoskeleton, and SEPT9 amplification enhances tumor cell survival by preventing nuclear damage.
SN - 0021-9525
SN - 1540-8140
ER -