Truncated ErbB2 receptor expression lowers nucleus stiffness and increases migration of breast cancer cells

Résumé fourni par la source

The mechanisms underlying mechanical differences among cancer cell lines with varying metastatic potential remain poorly understood, despite their clear therapeutic relevance. While comparisons between malignant and benign cell mechanics reveal systematic differences, these are difficult to attribute to specific molecular drivers, complicating mechanistic interpretation. Here, we investigate whether controlled expression of a single oncogene is sufficient to induce measurable morphological, mechanical, and migratory changes. Using atomic force microscopy-based microrheology on live-cell nuclei, we show that inducible expression of the oncogene p95HER2 in breast cancer cells leads to a reduced viscoelastic modulus and a lower transition frequency, consistent with nuclear fluidization. Fluorescence staining of the actin cytoskeleton reveals no detectable reorganization of actin at the nuclear region upon p95HER2 expression, suggesting that the mechanical changes originate primarily from alterations in the nucleus rather than from cytoskeletal remodeling. Consistent with this interpretation, western blotting of isolated nuclei demonstrates reduced lamin A/C expression in p95HER2-expressing cells, and measurements of isolated nuclei confirm that they are both taller and softer than control nuclei. Among Jeffrey’s model viscoelastic parameters, only the outer dashpot viscosity η 2 shows a marked reduction, suggesting it is specifically sensitive to lamin A/C levels. Cells expressing p95HER2 exhibit distinct morphological alterations and increased migratory capacity in a pore migration assay, quantified using deep-learning-based segmentation. Enhanced nuclear fluidity, driven at least in part by reduced lamin A/C, may facilitate migration by promoting efficient passage through endothelial barriers.

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