Lung Metastasis of Pancreatic Carcinoma is Regulated by TGFβ Signaling.

The molecular regulation of the lung metastasis of pancreatic carcinoma (PCC) is not completely understood. Here, we show that the levels of phosphorylated SMAD3, ZEB1, ZEB2, Snail1, and Snail2 were significantly higher in PCC with lung metastasis than in PCC without lung metastasis. Overexpression of TGFβ1 enhanced the invasiveness of PCC cells, while inhibition of TGFβ1 decreased the invasiveness of PCC cells, which appeared to be conducted by activated TGFβ receptor signaling-induced upregulation of ZEB1, ZEB2, Snail1, and Snail2, suggesting a process of epithelial-mesenchymal transition (EMT). Taken together, our study provides evidence that TGFβ receptor signaling-induced EMT may be responsible for the increased PCC invasiveness to enhance its lung metastasis.