Hedgehog Gli3 activator signal augments tumorigenicity of colorectal cancer via upregulation of adherence‐related genes

Hedgehog signal is re‐activated in several cancers. In this study, we examined the role of Gli3 on malignant phenotype of tumorigenicity for colorectal cancer and its relationship with p53, WNT and ERK / AKT signals. Gli3 expression was detected in HT 29 and SW 480 (p53‐mutant) cells, but not in DLD ‐1 (p53‐mutant) or HCT 116 (p53‐wild type) cells by reverse transcription‐polymerase chain reaction and immunocytochemistry. Full‐length Gli3 transfection increased anchor‐independent growth for all cells regardless of p53 status, with upregulation of adhesion‐related genes. Exogenous Sonic‐Hedgehog increased activator‐type of Gli3 and colony formation in Gli3‐positive HT 29 and SW 480 cells. After implantation of Gli3‐ FL or mock‐transfectant DLD ‐1 cells into SCID mice, tumor formation was highly observed in only Gli3‐ FL ‐transfectant group. In clinical specimens, Gli3 expression was detected in subsets of colorectal cancer and related with poorly‐differentiated histological type, while Sonic–Hedgehog was present with high incidence. In conclusion, activator Gli3 signal augments tumorigenicity of colorectal cancer irrespective of p53 status.