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 confirm the EMT phenomenon, we sequentially tested EMT markers, such as E-cadherin and vimentin, as well as mRNA and protein expressions. The RT-PCR and real-time quantitative PCR analysis (Fig. 2) indicated that the mRNA levels of vimentin and E-cadherin are significantly increased and suppressed by NE, respectively (P < 0.05). However, these effects can be reversed by the β2-AR antagonist ICI 118551. Western blot analysis (Fig. 3) showed that E-cadherin expression is significantly downregulated in the NE group compared with the control, whereas vimentin expression is substantially increased (P < 0.05). We also presented evidence that the β2-AR antagonist ICI 118551 can reverse NE-induced EMT, which is accompanied by the inhibition of vimentin protein expression and an increase in the expression of E-cadherin protein.
Affiliation: Department of General Surgery, Second Affiliated Hospital of Medical College, Xi'an Jiaotong University, Xi'an, China.