title: Novel regulatory program for norepinephrine-induced epithelial-mesenchymal transition in gastric adenocarcinoma cell lines.
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.
authors.affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Shan
authors.forename: Xijuan
authors.initials: X
authors.lastname: Cui
authors.forename: Wei
authors.initials: W
authors.lastname: Li
authors.forename: Wanrun
authors.initials: W
authors.lastname: Lin
authors.forename: Yiming
authors.initials: Y
authors.lastname: Li
authors.forename: Xi
authors.initials: X
authors.lastname: Chen
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D045744:Cell Line, Tumor / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects* / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism; D009638:Norepinephrine / Q000494:pharmacology*; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D014746:Vimentin / Q000235:genetics / Q000378:metabolism
chemical_list: D015415:Biomarkers; D015820:Cadherins; C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D018343:Receptors, Adrenergic, beta-2; D014746:Vimentin; D009638:Norepinephrine
keywords: EMT; HIF-1α; gastric adenocarcinoma; norepinephrine; β2-AR