Novel regulatory program for norepinephrine-induced epithelial-mesenchymal transition in gastric adenocarcinoma cell lines.
Bottom Line: 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.
Affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.Show MeSH
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Mentions: To further evaluate whether β2-AR activation induced by NE is essential for EMT to occur in gastric adenocarcinoma cells, the effects of β2-AR siRNA on the EMT of BGC-823 gastric adenocarcinoma cells were examined. BGC-823 was chosen because its cell line shows a higher expression of β2-AR. The efficacy of β2-AR siRNA to knockdown β2-AR mRNA and protein was confirmed by RT-PCR and Western blot, respectively. We observed that both β2-AR mRNA and protein levels (Fig. 6a,b) were barely detectable in β2-AR siRNA-transfected cells compared with control siRNA-transfected cells. Subsequently, NE did not induce the EMT phenomenon (Fig. 6c,d). Moreover, after treatment with NE in transfected cells, the expressions of HIF-1α, Snail, and vimentin were attenuated to a much greater extent than those of the control cells, whereas E-cadherin showed an opposite alteration (Fig. 6e,f). The results showed the critical effects of β2-AR activity in NE on the EMT of cancer cells.
Affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.