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

Abstract

Invasion by cancer cells is a critical 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 pharmacologic β-blockade or genetic knockout of the β2-adrenergic receptor. Our results identify a β2-adrenergic-Ca2+-actin axis as a novel regulator of cell deformability, and suggest that the relationship between cell mechanical properties and invasion may be dependent on context.