β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis
- Author(s)
- Kim, TH; Tran Le, MT; Oh, M; Vazquez-Hidalgo, E; Chavez, B; Lamkin, DM; Abdou, A; Tan, XHM; Christodoulides, A; Farris, CM; Lee, C; Chiou, PY; Sloan, EK; Katira, P; Rowat, AC;
- Details
- Publication Year 2025-06-20,Volume 28,Issue #6,Page 112676
- Journal Title
- iScience
- Publication Type
- Research article
- 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-ROCK-non-muscle myosin II (NMII) signaling axis that modulates the mechanical behaviors of MDA-MB-231(HM) and MDA-MB-468 cells. These findings provide insight into how stress signaling regulates cancer cell mechanics and suggest potential targets to block metastasis in triple-negative breast cancer.
- Publisher
- Elsevier
- Keywords
- Cell biology; Functional aspects of cell biology; Mechanobiology
- Department(s)
- Surgical Oncology
- Publisher's Version
- https://doi.org/10.1016/j.isci.2025.112676
- Open Access at Publisher's Site
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- Refer to copyright notice on published article.
Creation Date: 2025-07-31 02:10:16
Last Modified: 2025-07-31 02:10:50