The Journal of Cell Biology· 2026Q1
Septins buffer actomyosin forces to protect the nucleus from genotoxic mechanical stress
- 1citations
- Q1SCImago
- 2026year
Short summary
Septin filaments, particularly SEPT9, buffer actomyosin forces to prevent nuclear damage during cell migration through confined spaces.
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Key points
- Septin filaments buffer actomyosin forces acting on the nucleus during confined cell migration.
- SEPT9 depletion increases actin stress and causes nuclear envelope ruptures and DNA breaks.
- SEPT9 amplification correlates with reduced genomic alterations in aggressive breast tumors.
- Septins act as a mechanoprotective element, preventing nuclear damage.
AI-generated from the title and abstract; the full text is not read.
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.
The authors' abstract, as published at the source. The Journal of Cell Biology, 2026 · DOI ↗
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Field: Cell Biology
Cell BiologyBiochemistry, Genetics and Molecular Biology