title: Down-regulation of Gli-1 inhibits hepatocellular carcinoma cell migration and invasion.
abstract: Glioma-associated oncogene homolog-1 (Gli-1) is considered a marker of Hedgehog pathway activation and is associated with the progression of several cancers. We have previously reported that Gli-1 was correlated with invasion and metastasis in hepatocellular carcinoma (HCC). However, the exact roles and mechanisms of Gli-1 in HCC invasion are unclear. In this study, we found that small interfering RNA mediated down-regulation of Gli-1 expression significantly suppressed adhesion, motility, migration, and invasion of both SMMC-7721 and SK-Hep1 cells. Furthermore, down-regulation of Gli-1 significantly reduced expressions and activities of both matrix metalloproteinase (MMP)-2 and MMP-9. In addition, we found that down-regulation of Gli-1 resulted in up-regulation of E-cadherin and concomitant down-regulation of Snail and Vimentin, consistent with inhibition of epithelial-mesenchymal transition (EMT). Taken together, our results suggest that down-regulation of Gli-1 suppresses HCC cell migration and invasion likely through inhibiting expressions and activations of MMP-2, 9 and blocking EMT.
authors.affiliation: Department of Gastrointesinal Surgery, The First Affiliated Hospital of Guangzhou Medical University, Guangzhou, 510120, People's Republic of China, hychenjs@126.com.
authors.forename: Jing-Song
authors.initials: JS
authors.lastname: Chen
authors.forename: Hua-Shu
authors.initials: HS
authors.lastname: Li
authors.forename: Jiong-Qiang
authors.initials: JQ
authors.lastname: Huang
authors.forename: Long-Juan
authors.initials: LJ
authors.lastname: Zhang
authors.forename: Xi-Lin
authors.initials: XL
authors.lastname: Chen
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.forename: Jian
authors.initials: J
authors.lastname: Lei
authors.forename: Ju-Tao
authors.initials: JT
authors.lastname: Feng
authors.forename: Qin
authors.initials: Q
authors.lastname: Liu
authors.forename: Xiao-Hui
authors.initials: XH
authors.lastname: Huang
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D020778:Matrix Metalloproteinase 2 / Q000096:biosynthesis; D020780:Matrix Metalloproteinase 9 / Q000096:biosynthesis; D009361:Neoplasm Invasiveness / Q000235:genetics; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000037:antagonists & inhibitors / Q000235:genetics*; D000071676:Zinc Finger Protein GLI1
chemical_list: C400551:GLI1 protein, human; D034741:RNA, Small Interfering; D014157:Transcription Factors; D000071676:Zinc Finger Protein GLI1; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9