Upregulation of Twist is involved in Gli1 induced migration and invasion of hepatocarcinoma cells

Hedgehog (Hh) signaling is involved in the progression of hepatocellular carcinoma (HCC), while its detailed mechanisms are not well illustrated. Our present study revealed that the expression of Gli1, while not Gli2 or Gli3, is significantly increased in HCC cell lines and 20/28 (71.4%) HCC tissues as compared with their corresponding controls. Over expression of Gli1 can promote the migration, invasion and epithelial-mesenchymal transition (EMT) of HCC cells. Gli1 can increase the expression of Twist, while not other EMT transcription factors such as Snail, ZEB1 or Slug. Gli1 increases the transcription of Twist while it has no significant effect on the protein or mRNA stability. Chromatin immunoprecipitation-polymerase chain reaction confirms that Gli1 can directly bind to the promoter of Twist, in which the third binding site is essential for Gli1 induced transcription. Collectively, our data suggest that upregulation of Twist is involved in Gli1 induced migration and invasion of HCC cells.