title: The glioma-associated oncogene homolog 1 promotes epithelial--mesenchymal transition in human esophageal squamous cell cancer by inhibiting E-cadherin via Snail.
abstract: The glioma-associated oncogene homolog 1 (GLI1) family of zinc finger transcription factors is the nuclear mediator of the Hedgehog pathway that regulates genes essential for various stages of tumor development and progression. However, the role and mechanism by which high expression of GLI1 contributes to the invasion and metastasis of human esophageal squamous cell cancer (ESCC) has not been fully elucidated. In the present study, we demonstrated that GLI1 was over-expressed in human ESCC tissues, especially in ESCC tissues with deep invasion and lymph-node metastasis. Moreover, GLI1 was also over-expressed in ESCC cell lines and correlated with the aggressiveness of ESCC cell lines. In addition, GLI signaling pathway agonist purmorphamine could increase the invasion and metastasis ability of ESCC cells in vitro. There is increasing evidence for the contribution of epithelial-mesenchymal transition (EMT) to ESCC invasion and metastasis, therefore we investigated GLI1's role in EMT. Our results showed that high expression of GLI1 dampened expression of E-cadherin and enhanced the expression of Vimentin, and it also improved the expression of Snail, indicative of its role in EMT occurrence. Mechanistic studies showed that down-expression of Snail reversed GLI1 activation-regulated expression of EMT markers, suggesting the role of Snail in GLI1-mediated EMT. Taken together, our results had revealed that GLI1 could participate in the invasion and metastasis of ESCC through EMT. These studies indicated that in ESCC, GLI1 could be a useful target for cancer prevention and therapy.
authors.affiliation: Department of Oncology, the First Affiliated Hospital of Zhengzhou University, Zhengzhou, China.
authors.forename: S
authors.initials: S
authors.lastname: Min
authors.forename: X
authors.initials: X
authors.lastname: Xiaoyan
authors.forename: P
authors.initials: P
authors.lastname: Fanghui
authors.forename: W
authors.initials: W
authors.lastname: Yamei
authors.forename: Y
authors.initials: Y
authors.lastname: Xiaoli
authors.forename: W
authors.initials: W
authors.lastname: Feng
mesh_terms: D015703:Antigens, CD; D015820:Cadherins / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition; D004938:Esophageal Neoplasms / Q000378:metabolism* / Q000473:pathology; D000077277:Esophageal Squamous Cell Carcinoma; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D009361:Neoplasm Invasiveness; D034741:RNA, Small Interfering / Q000235:genetics; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014746:Vimentin / Q000235:genetics / Q000378:metabolism; D000071676:Zinc Finger Protein GLI1
chemical_list: D015703:Antigens, CD; C513384:CDH1 protein, human; D015820:Cadherins; C400551:GLI1 protein, human; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D014746:Vimentin; D000071676:Zinc Finger Protein GLI1