β2-Adrenergic Receptor Signaling Pathway Stimulates the Migration and Invasion of Cancer Cells via Src Activation

Chronic stress has been reported to stimulate the release of catecholamines, including norepinephrine (NE) and epinephrine (E), which promote cancer progression by activating the adrenergic receptor (AR). Although previous studies showed that beta 2-AR mediated chronic stress-induced tumor growth and metastasis, the underlying mechanism has not been fully explored. In this study, we aimed to investigate the molecular mechanism by which beta 2-AR exerts a pro-metastatic function in hepatocarcinoma (HCC) cells and breast cancer (BC) cells. Our results showed that Hep3B human HCC cells and MDA-MB-231 human BC cells exhibited the highest ADRB2 expression among diverse HCC and BC cell lines. NE, E, and isoprenaline (ISO), adrenergic agonists commonly increased the migration and invasion of Hep3B cells and MDA-MB-231 cells. The phosphorylation level of Src was significantly increased by E/NE. Dasatinib, a Src kinase inhibitor, blocked E/NE-induced migration and invasion, indicating that AR agonists enhanced the mobility of cancer cells by activating Src. ADRB2 knockdown attenuated E/NE-induced Src phosphorylation, as well as the metastatic ability of cancer cells, suggesting the essential role of beta 2-AR. Taken together, our results demonstrate that chronic stress-released catecholamines promoted the migration and invasion of HCC cells and BC cells via beta 2-AR-mediated Src activation.

Automated summary

Chronic stress-induced catecholamines promote the migration and invasion of hepatocarcinoma and breast cancer cells through activation of the β2-AR and Src signaling pathway.