β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis
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<sup>HM</sup> 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<sup>HM</sup> 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.
Authors
- Erica K. Sloan (ORCID: https://orcid.org/0000-0002-2355-1433)
- Xing Haw Marvin Tan
- Minh-Tam Tran Le
- Amy C. Rowat (ORCID: https://orcid.org/0000-0001-5800-5320)
- Alexei Christodoulides (ORCID: https://orcid.org/0000-0003-0685-3154)
- Donald M. Lamkin
- Esteban Vazquez-Hidalgo
- Mi-Jung Oh (ORCID: https://orcid.org/0000-0002-4658-9338)
- Carly M. Farris (ORCID: https://orcid.org/0000-0002-8277-8531)
- Pei‐Yu Chiou (ORCID: https://orcid.org/0000-0003-4677-2447)
- Parag Katira (ORCID: https://orcid.org/0000-0001-9873-5117)
- Alexander Abdou
- Tae-Hyung Kim (ORCID: https://orcid.org/0000-0002-5045-4401)
- Chang‐Hoon Lee (ORCID: https://orcid.org/0000-0002-4031-3795)
- Bertha Chávez (ORCID: https://orcid.org/0000-0002-2020-7741)
Institutions
- Salk Institute for Biological Studies (US)
- California NanoSystems Institute (US)
- University of California, Los Angeles (US)
- University of New Mexico (US)
- San Diego State University (US)
- Discovery Institute (US)
- Peter MacCallum Cancer Centre (AU)
- Broad Center (US)
- Monash University (AU)
- The University of Texas Southwestern Medical Center (US)
Publication Details
- Journal
- iScience
- Published
- 2025-05-15
- DOI
- https://doi.org/10.1016/j.isci.2025.112676
- Citations
- 3
- Primary Topic
- Cancer, Stress, Anesthesia, and Immune Response
- Type
- article
- Field-Weighted Citation Impact
- 4.41
Funders
- National Science Foundation
- METAvivor
- National Cancer Institute
- National Institute of General Medical Sciences
- Army Research Office
- Jonsson Cancer Center Foundation