Adrenaline promotes epithelial-to-mesenchymal transition via HuR-TGFβ regulatory axis in pancreatic cancer cells and the implication in cancer prognosis

摘要

Abstract Psychological stress has recently been described as a risk factor in the development of pancreatic cancer. Here, we reported that increased neurotransmitter adrenaline was associated with the poor survival in pancreatic cancer patients. Moreover, in the cell model study, we found adrenaline promoted pancreatic cell PANC-1 migration in a dose dependent manner. Block of the β2-adrenoreceptor with ICI118,551, significantly reduced cell migration. Further study found that adrenaline induced a cytoplasmic translocation of RNA binding protein HuR, which in turn activated TGFβ, as shown by the SBE luciferase assay and phosphorylation of Smad2/3. Either HuR knockdown or TGFβ inhibition reduced cell migration induced by adrenaline. Taken together, our study here revealed that adrenaline–HuR–TGFβ regulatory axis at least partially contributes to the psychological stress induced metastasis in PANC-1 cells, shedding light on therapeutic targeting psychological stress in improving the prognosis of pancreatic cancer. Highlights ? Adrenaline negatively correlates with the survival of pancreatic cancer patients. ? Adrenaline promotes pancreatic cancer cell migration via β2-adrenoceptor activation. ? Adrenaline induces activation of TGFβ via RNA binding protein HuR. ? HuR-TGFβ axis contributes to cell migration induced by adrenaline.