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An oversimplified view in the literature is that cancer cells become more deformable as they become more invasive. \u03b2-adrenergic receptor (\u03b2AR) signaling drives invasion and metastasis, but the effects on cell deformability are not known. Here, we show that activation of \u03b2-adrenergic signaling by \u03b2AR agonists reduces the deformability of highly metastatic human breast cancer cells, and that these stiffer cells are more invasive in vitro. We find that \u03b2AR activation also reduces the deformability of ovarian, prostate, melanoma and leukemia cells. Mechanistically, we show that \u03b2AR-mediated cell stiffening depends on the actin cytoskeleton and myosin II activity. These changes in cell deformability can be prevented by pharmacological \u03b2-blockade or genetic knockout of the \u03b22-adrenergic receptor. Our results identify a \u03b22-adrenergic\u2013Ca2+\u2013actin axis as a new regulator of cell deformability, and suggest that the relationship between cell mechanical properties and invasion might be dependent on context.<\/jats:p>","DOI":"10.1242\/jcs.194803","type":"journal-article","created":{"date-parts":[[2016,11,15]],"date-time":"2016-11-15T01:50:19Z","timestamp":1479174619000},"page":"4563-4575","source":"Crossref","is-referenced-by-count":97,"title":["Cancer cells become less deformable and more invasive with activation of \u03b2-adrenergic signaling"],"prefix":"10.1242","volume":"129","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5045-4401","authenticated-orcid":false,"given":"Tae-Hyung","family":"Kim","sequence":"first","affiliation":[{"name":"University of California 1 Department of Integrative Biology and Physiology , , Los Angeles 90095 , USA"},{"name":"Semel Institute for Neuroscience and Human Behavior, University of California 2 , Los Angeles 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Navjot Kaur","family":"Gill","sequence":"additional","affiliation":[{"name":"University of California 1 Department of Integrative Biology and Physiology , , Los Angeles 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendra D.","family":"Nyberg","sequence":"additional","affiliation":[{"name":"University of California 1 Department of Integrative Biology and Physiology , , Los Angeles 90095 , USA"},{"name":"University of California 3 Department of Bioengineering , , Los Angeles 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelyn V.","family":"Nguyen","sequence":"additional","affiliation":[{"name":"University of California 1 Department of Integrative Biology and Physiology , , Los Angeles 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sophia V.","family":"Hohlbauch","sequence":"additional","affiliation":[{"name":"Asylum Research, an Oxford Instruments Company 4 , Santa Barbara, CA 93117 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicholas A.","family":"Geisse","sequence":"additional","affiliation":[{"name":"Asylum Research, an Oxford Instruments Company 4 , Santa Barbara, CA 93117 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cameron J.","family":"Nowell","sequence":"additional","affiliation":[{"name":"Monash Institute of Pharmaceutical Sciences, Monash University 5 Drug Discovery Biology Theme , , Parkville, Victoria 3052 , Australia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erica K.","family":"Sloan","sequence":"additional","affiliation":[{"name":"Semel Institute for Neuroscience and Human Behavior, University of California 2 , Los Angeles 90095 , USA"},{"name":"Monash Institute of Pharmaceutical Sciences, Monash University 5 Drug Discovery Biology Theme , , Parkville, Victoria 3052 , Australia"},{"name":"Peter MacCallum Cancer Centre 6 Division of Cancer Surgery , , Melbourne, Victoria 3000 , Australia"},{"name":"UCLA Jonsson Comprehensive Cancer Center, University of California 7 , Los Angeles 90095 , USA"},{"name":"UCLA AIDS Institute, University of California 8 , Los Angeles 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5800-5320","authenticated-orcid":false,"given":"Amy C.","family":"Rowat","sequence":"additional","affiliation":[{"name":"University of California 1 Department of Integrative Biology and Physiology , , Los Angeles 90095 , USA"},{"name":"University of California 3 Department of Bioengineering , , Los Angeles 90095 , USA"},{"name":"UCLA Jonsson Comprehensive Cancer Center, University of California 7 , Los Angeles 90095 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"237","reference":[{"key":"2024061400044024400_JCS194803C1","doi-asserted-by":"publisher","first-page":"C792","DOI":"10.1152\/ajpcell.00425.2001","article-title":"Stiffness changes in cultured airway smooth muscle cells","volume":"283","author":"An","year":"2002","journal-title":"Am. 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