Background: The Hedgehog signaling pathway and its key target effector Gli1 are linked closely to the development of the epithelial to mesenchymal transition (EMT) in many cancers. The definite function of Gli1 in regulating the EMT of pancreatic cancer (PC), however, is still unclear.
Methods: At the cell and tissue levels, we investigated the role of Gli1 in the initiation of EMT in PC with and without external stimulus treatments.
Results: The immunohistochemistry results showed that Gli1 was associated positively with MMP9 but not with E-cad or Vimentin. Gli1 expression was associated positively with tumor T (P = .025) and Union for International Cancer Control stage (P = .032), whereas MMP9 expression was associated positively with lymph node metastasis (P = .017) and Union for International Cancer Control stage (P = .006). Furthermore, patients with Gli1 and MMP9 coexpression had poor overall survival (P = .015). Silencing of Gli1 alone without external stimulus had no effect on EMT but inhibited transforming growth factor-beta1 (TGFβ1)- and epidermal growth factor (EGF)-induced EMT in PANC-1, AsPC-1, and BxPC-3 PC cell lines, along with the inhibition of TGFβ1- and EGF-induced EMT-like cell morphology and invasion, down-regulation of E-cad, and up-regulation of MMP9 and Vimentin in those 3 cell lines, respectively.
Conclusion: Gli1 silencing alone has no effect on EMT initiation; however, it exerts a protumor role in the aggressive invasion of PC cells by promoting TGFβ1- and EGF-induced EMT.
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