Norepinephrine and epinephrine, catecholamine hormones that are major mediators for chronic stress-induced cancers, are implicated in the progression of a number of cancer cells, including gastric adenocarcinoma. However, the underlying mechanisms of these hormones have not been well elucidated. Epithelial-mesenchymal transition (EMT) is a crucial event responsible for cancer cell invasion and metastasis. The hypothesis regarding whether the promotive effects of norepinephrine (NE) on cancer are in part due to its ability to induce an EMT program has not been proven. In this study, we show that NE does not only obviously induce EMT alterations in the morphological characteristics of gastric adenocarcinoma cells, but also increases the markers of EMT, including vimentin expression, and decreases E-cadherin expression, further resulting in cell motility and invasiveness. We also reveal that these actions are mainly mediated through the activation of β2 -AR-HIF-1α-Snail signaling pathways. In summary, this study implies that NE induces EMT in gastric adenocarcinoma through the regulation of β2 -AR-HIF-1α-Snail activity. The data provide a new perspective on chronic stress in a negative social and psychological state, which may be a risk factor for cancer development and progression.
Keywords: EMT; HIF-1α; gastric adenocarcinoma; norepinephrine; β2-AR.
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.