Cancer cells become less deformable and more invasive with activation of ß-adrenergic signaling.
J Cell Sci
; 129(24): 4563-4575, 2016 12 15.
Article
in En
| MEDLINE
| ID: mdl-27875276
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. ß-adrenergic receptor (ßAR) signaling drives invasion and metastasis, but the effects on cell deformability are not known. Here, we show that activation of ß-adrenergic signaling by ßAR agonists reduces the deformability of highly metastatic human breast cancer cells, and that these stiffer cells are more invasive in vitro We find that ßAR activation also reduces the deformability of ovarian, prostate, melanoma and leukemia cells. Mechanistically, we show that ßAR-mediated cell stiffening depends on the actin cytoskeleton and myosin II activity. These changes in cell deformability can be prevented by pharmacological ß-blockade or genetic knockout of the ß2-adrenergic receptor. Our results identify a ß2-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.
Key words
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Receptors, Adrenergic, beta-2
/
Neoplasms
Type of study:
Prognostic_studies
Limits:
Humans
Language:
En
Journal:
J Cell Sci
Year:
2016
Document type:
Article
Affiliation country: