title: Hedgehog Gli3 activator signal augments tumorigenicity of colorectal cancer via upregulation of adherence-related genes.
abstract: 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 HT29 and SW480 (p53-mutant) cells, but not in DLD-1 (p53-mutant) or HCT116 (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 HT29 and SW480 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.
authors.affiliation: Department of Cancer Therapy and Research, Kyushu University, Fukuoka, Japan.
authors.forename: Hironori
authors.initials: H
authors.lastname: Iwasaki
authors.forename: Kenji
authors.initials: K
authors.lastname: Nakano
authors.forename: Kentaro
authors.initials: K
authors.lastname: Shinkai
authors.forename: Yumi
authors.initials: Y
authors.lastname: Kunisawa
authors.forename: Minako
authors.initials: M
authors.lastname: Hirahashi
authors.forename: Yoshinao
authors.initials: Y
authors.lastname: Oda
authors.forename: Hideya
authors.initials: H
authors.lastname: Onishi
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Katano
mesh_terms: D000818:Animals; D015815:Cell Adhesion Molecules / Q000235:genetics*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D020868:Gene Silencing; D016158:Genes, p53; D053823:Hedgehog Proteins / Q000378:metabolism*; D006801:Humans; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism*; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009368:Neoplasm Transplantation; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D015398:Signal Transduction; D014162:Transfection; D014183:Transplantation, Heterologous; D015854:Up-Regulation; D000074290:Zinc Finger Protein Gli3
chemical_list: D015815:Cell Adhesion Molecules; C065683:GLI3 protein, human; D053823:Hedgehog Proteins; D051741:Kruppel-Like Transcription Factors; D009419:Nerve Tissue Proteins; D000074290:Zinc Finger Protein Gli3