Crosstalk of Hedgehog and Wnt pathways is a possible therapeutic target of gastric cancer

Morphogenic signals like Hedgehog (Hh) and Wnt are reported to play critical roles in the progression of gastric cancer. A close association between Hh and Wnt signaling pathways has also been reported in embryonic and adult tissues. However, few studies have investigated the role of crosstalk between these pathways in gastric cancer. We aimed to assess the crosstalk between these signaling pathways. Nuclear β-catenin staining and nuclear Gli1 staining were used as markers of activated Wnt and Hh signaling, respectively. In gastric carcinoma tissues, Wnt pathway activation and Hh pathway activation were significantly higher in differentiated-type and undifferentiated-type carcinoma cells, respectively. Furthermore, our study indicates for the first time that Wnt pathway activation is inversely correlated with Hh pathway activation. When AGS gastric cancer cells, in which Wnt signaling is constitutively active, were used as a target cell line, Gli1 overexpression suppressed Wnt transcriptional activity, nuclear β-catenin accumulation and proliferation of AGS cells. Knock-down of β-catenin by siRNA suppressed Wnt pathway activity and proliferation of AGS cells. Our data may provide some clues for the treatment of gastric cancer associated with Wnt signaling activation.