title: Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling.
abstract: Invasion by cancer cells is a crucial step in metastasis. An oversimplified view in the literature is that cancer cells become more deformable as they become more invasive. β-adrenergic receptor (βAR) signaling drives invasion and metastasis, but the effects on cell deformability are not known. Here, we show that activation of β-adrenergic signaling by βAR agonists reduces the deformability of highly metastatic human breast cancer cells, and that these stiffer cells are more invasive in vitro We find that βAR activation also reduces the deformability of ovarian, prostate, melanoma and leukemia cells. Mechanistically, we show that βAR-mediated cell stiffening depends on the actin cytoskeleton and myosin II activity. These changes in cell deformability can be prevented by pharmacological β-blockade or genetic knockout of the β2-adrenergic receptor. Our results identify a β2-adrenergic-Ca2+-actin axis as a new regulator of cell deformability, and suggest that the relationship between cell mechanical properties and invasion might be dependent on context.
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles 90095, USA.|Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles 90095, USA.
authors.forename: Tae-Hyung
authors.identifier: 0000-0002-5045-4401
authors.initials: TH
authors.lastname: Kim
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles 90095, USA.
authors.forename: Navjot Kaur
authors.initials: NK
authors.lastname: Gill
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles 90095, USA.|Department of Bioengineering, University of California, Los Angeles 90095, USA.
authors.forename: Kendra D
authors.initials: KD
authors.lastname: Nyberg
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles 90095, USA.
authors.forename: Angelyn V
authors.initials: AV
authors.lastname: Nguyen
authors.affiliation: Asylum Research, an Oxford Instruments Company, Santa Barbara, CA 93117, USA.
authors.forename: Sophia V
authors.initials: SV
authors.lastname: Hohlbauch
authors.affiliation: Asylum Research, an Oxford Instruments Company, Santa Barbara, CA 93117, USA.
authors.forename: Nicholas A
authors.initials: NA
authors.lastname: Geisse
authors.affiliation: Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.
authors.forename: Cameron J
authors.initials: CJ
authors.lastname: Nowell
authors.affiliation: Semel Institute for Neuroscience and Human Behavior, University of California, Los Angeles 90095, USA.|Drug Discovery Biology Theme, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria 3052, Australia.|Division of Cancer Surgery, Peter MacCallum Cancer Centre, Melbourne, Victoria 3000, Australia.|UCLA Jonsson Comprehensive Cancer Center, University of California, Los Angeles 90095, USA.|UCLA AIDS Institute, University of California, Los Angeles 90095, USA.
authors.forename: Erica K
authors.initials: EK
authors.lastname: Sloan
authors.affiliation: Department of Integrative Biology and Physiology, University of California, Los Angeles 90095, USA rowat@ucla.edu.|Department of Bioengineering, University of California, Los Angeles 90095, USA.|UCLA Jonsson Comprehensive Cancer Center, University of California, Los Angeles 90095, USA.
authors.forename: Amy C
authors.identifier: 0000-0001-5800-5320
authors.initials: AC
authors.lastname: Rowat
mesh_terms: D000199:Actins / Q000378:metabolism; D002118:Calcium / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D006801:Humans; D007545:Isoproterenol / Q000494:pharmacology; D008954:Models, Biological; D009361:Neoplasm Invasiveness; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology*; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D000199:Actins; D018343:Receptors, Adrenergic, beta-2; D007545:Isoproterenol; D002118:Calcium
keywords: Atomic force microscopy; Cancer; Cell mechanical properties; Invasion; Mechanotype; Parallel microfiltration; β2-adrenergic receptor