Novel regulatory program for norepinephrine‐induced epithelial–mesenchymal transition in gastric adenocarcinoma cell lines

Cancer Science

Tao Shan¹  Xijuan Cui³  Wei Li²  Wanrun Lin⁴  Yiming Li¹  Xi Chen¹ 

[1] Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China;Graduate School, Fourth Military Medical University, Xi'an, China;Department of General Surgery, First Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China;Department of Pathology, Shandong Provincial Hospital, Ji'nan, China

关键词: β2‐AR;    EMT;    gastric adenocarcinoma;    HIF‐1α;    norepinephrine;   

DOI  :  10.1111/cas.12438

来源: Wiley

【 摘 要 】

Abstract

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.

【 授权许可】

CC BY-NC   
© 2014 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Creative Commons Attribution-NonCommercial License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes.