Cancer cells become less deformable and more invasive with activation of β-adrenergic signaling

Tae-Hyung Kim, Navjot Kaur Gill, Kendra D. Nyberg, Angelyn V. Nguyen, Sophia V. Hohlbauch, Nicholas A. Geisse, Cameron Nowell, Erica Sloan, Amy C. Rowat

Research output: Contribution to journalArticleResearchpeer-review

38 Citations (Scopus)

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 βARmediated 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.

Original languageEnglish
Pages (from-to)4563-4575
Number of pages13
JournalJournal of Cell Science
Volume129
Issue number24
DOIs
Publication statusPublished - 2016

Keywords

  • Atomic force microscopy
  • Cancer
  • Cell mechanical properties
  • Invasion
  • Mechanotype
  • Parallel microfiltration
  • β-adrenergic receptor

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