Lamin B receptor upregulation in metastatic melanoma causes nuclear envelope fragility in confined migration during cancer invasion.

ABSTRACT: Cancer cells migrate through regions of tissue confinement during metastasis, causing nuclear envelope (NE) rupture, which generates heritable DNA damage and disease aggression. We sought to determine if NE rupture was intrinsic to malignant transformation and seek a mechanistic cause. We found that metastatic cells from multiple cancer subtypes have increased NE fragility in confinement compared to their benign counterparts. Meta-analysis of transcriptomic data from clinical samples of melanoma progression together with an siRNA-based live-cell confinement screen revealed that lamin B receptor (LBR) transcriptional upregulation correlates with melanoma progression and NE fragility. LBR is an inner nuclear membrane protein (INM) that scaffolds lamins and chromatin and has sterol reductase

SUBMITTER: Baird MA 

PROVIDER: S-EPMC12933115 | biostudies-literature | 2026 Feb

REPOSITORIES: biostudies-literature