The β2-adrenoceptor activates a positive cAMP-calcium feedforward loop to drive breast cancer cell invasion.

ABSTRACT: Activation of the sympathetic nervous system by stress increases breast cancer metastasis in vivo. Preclinical studies suggest that stress activates β-adrenoceptors (βARs) to enhance metastasis from primary tumors and that β-blockers may be protective in breast cancer. However, the subtype of βAR that mediates this effect, as well as the signaling mechanisms underlying increased tumor cell dissemination, remain unclear. We show that the β2AR is the only functionally relevant βAR subtype in the highly metastatic human breast cancer cell line MDA-MB-231HM. β2AR activation results in elevated cAMP (formoterol pEC50 9.86 ± 0.32), increased intracellular Ca(2+) (formoterol pEC50 8.20 ± 0.33) and reduced phosphorylated ERK (pERK; formoterol pIC50 11.62 ± 0.31). We demonstrate that a highly ampli

SUBMITTER: Pon CK 

PROVIDER: S-EPMC4750412 | biostudies-literature | 2016 Mar

REPOSITORIES: biostudies-literature