β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis
Summary: 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...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-06-01
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| Series: | iScience |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S258900422500937X |
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| author | 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 |
| author_facet | 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 |
| author_sort | Tae-Hyung Kim |
| collection | DOAJ |
| description | Summary: 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-231HM 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-231HM 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. |
| format | Article |
| id | doaj-art-cf3448a244e244f7ba6e10367cebe66a |
| institution | DOAJ |
| issn | 2589-0042 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | iScience |
| spelling | doaj-art-cf3448a244e244f7ba6e10367cebe66a2025-08-20T03:18:32ZengElsevieriScience2589-00422025-06-0128611267610.1016/j.isci.2025.112676β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axisTae-Hyung Kim0Minh-Tam Tran Le1Mijung Oh2Esteban Vazquez-Hidalgo3Bryanna Chavez4Donald M. Lamkin5Alexander Abdou6Xing Haw Marvin Tan7Alexei Christodoulides8Carly M. Farris9Changhoon Lee10Pei-Yu Chiou11Erica K. Sloan12Parag Katira13Amy C. Rowat14Department of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM, USA; Corresponding authorDepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USADepartment of Pathology, School of Medicine, University of New Mexico, Albuquerque, NM, USAMechanical Engineering Department, San Diego State University, San Diego, CA, USA; Computational Science Research Center, San Diego State University, San Diego, CA, USADepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USACousins Center for Psychoneuroimmunology, Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles, Los Angeles, CA, USADepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USADepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA; Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA, USADepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USAMechanical Engineering Department, San Diego State University, San Diego, CA, USA; Computational Science Research Center, San Diego State University, San Diego, CA, USADepartment of Neuroscience, Peter O’Donnell Jr. Brain Institute, University of Texas Southwestern Medical Center, Dallas, TX, USADepartment of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA; Department of Mechanical and Aerospace Engineering, University of California, Los Angeles, Los Angeles, CA, USADrug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC 3052, Australia; Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, VIC 3052, AustraliaMechanical Engineering Department, San Diego State University, San Diego, CA, USA; Computational Science Research Center, San Diego State University, San Diego, CA, USADepartment of Integrative Biology and Physiology, University of California, Los Angeles, Los Angeles, CA, USA; Department of Bioengineering, University of California, Los Angeles, Los Angeles, CA, USA; UCLA Jonsson Comprehensive Cancer Center, University of California, Los Angeles, Los Angeles, CA, USA; Eli and Edythe Broad Center of Regenerative Medicine and Stem Cell Research, University of California, Los Angeles, Los Angeles, CA, USA; California NanoSystems Institute, University of California, Los Angeles, Los Angeles, CA, USA; Corresponding authorSummary: 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-231HM 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-231HM 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.http://www.sciencedirect.com/science/article/pii/S258900422500937XMechanobiologyCell biologyFunctional aspects of cell biology |
| spellingShingle | 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 β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis iScience Mechanobiology Cell biology Functional aspects of cell biology |
| title | β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis |
| title_full | β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis |
| title_fullStr | β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis |
| title_full_unstemmed | β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis |
| title_short | β-adrenergic signaling modulates breast cancer cell mechanical behaviors through a RhoA-ROCK-myosin II axis |
| title_sort | β adrenergic signaling modulates breast cancer cell mechanical behaviors through a rhoa rock myosin ii axis |
| topic | Mechanobiology Cell biology Functional aspects of cell biology |
| url | http://www.sciencedirect.com/science/article/pii/S258900422500937X |
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