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

Tae-Hyung Kim; Minh-Tam Tran Le; Mijung Oh; Esteban Vazquez-Hidalgo; Bryanna Chavez; Donald M Lamkin; Alexander Abdou; Xing Haw Marvin Tan; Alexei Christodoulides; Carly M Farris; Changhoon Lee; Pei-Yu Chiou; Erica K Sloan; Parag Katira; Amy C Rowat

doi:10.1016/j.isci.2025.112676

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

iScience. 2025 May 15;28(6):112676. doi: 10.1016/j.isci.2025.112676. eCollection 2025 Jun 20.

Authors

Tae-Hyung Kim^{1

2}, Minh-Tam Tran Le³, Mijung Oh², Esteban Vazquez-Hidalgo^{4

5}, Bryanna Chavez¹, Donald M Lamkin⁶, Alexander Abdou¹, Xing Haw Marvin Tan^{3

7}, Alexei Christodoulides¹, Carly M Farris^{4

5}, Changhoon Lee⁸, Pei-Yu Chiou^{3

7}, Erica K Sloan^{9

10}, Parag Katira^{4

5}, Amy C Rowat^{1

3

11

12

13}

Affiliations

¹ Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA.
² Department of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM, USA.
³ Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA.
⁴ Mechanical Engineering Department, San Diego State University, San Diego, CA, USA.
⁵ Computational Science Research Center, San Diego State University, San Diego, CA, USA.
⁶ Cousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USA.
⁷ Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA, USA.
⁸ Department of Neuroscience, Peter O'Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USA.
⁹ Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia.
¹⁰ Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC 3052, Australia.
¹¹ UCLA Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA.
¹² Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA.
¹³ California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA.

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.

Keywords: Cell biology; Functional aspects of cell biology; Mechanobiology.