β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis.

ABSTRACT: The ability of cancer cells to deform and generate force is implicated in metastasis. We previously showed that β-adrenergic agonists increase cancer cell stiffness, which was associated with enhanced motility and invasion. Here, we investigate how β-adrenoceptor (βAR) activation alters the mechanical behaviors of triple-negative breast cancer cells. We find that βAR activation increases traction forces in metastatic MDA-MB-231^HM and MDA-MB-468 cells, but not in non-tumorigenic MCF10A cells. Using computational modeling, we show that βAR activation increases the number of active myosin motors via myosin light chain phosphorylation. To identify molecular regulators, we use a deformability assay to screen for pharmacologic and genetic perturbations. Our results define a βAR-RhoA-R

SUBMITTER: Kim TH 

PROVIDER: S-EPMC12164020 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature