Mechanical Stress Induces Nuclear Envelope Rupture in Melanoma Cells to Reorganize Tumor-Stromal Interactions.

Recurrent macroscopic mechanical stress causes nuclear envelope rupture in melanoma cells and increases LRRC15-positive myofibroblasts in mouse models.

• Why it matters: Understanding how external mechanical forces impact tumor microenvironments can reveal mechanisms behind tumor progression, metastasis, and therapy resistance.
• What they did: The study applied mechanical stress to mouse plantar melanoma models and used inducible Lmna deletion, co-culture experiments, and human sample analysis to examine effects on nuclear integrity, stromal cell changes, and tumor behavior.
• The result: Mechanical stress-induced nuclear envelope rupture and stromal remodeling correlated with increased lymph node metastasis and immunotherapy resistance, suggesting mechanical forces influence melanoma progression through cellular and microenvironmental alterations.