title: Integrin β4 promotes cell invasion and epithelial-mesenchymal transition through the modulation of Slug expression in hepatocellular carcinoma.
abstract: Integrin β4 (ITGB4) is a transmembrane receptor involved in tumorigenesis and the invasiveness of many cancers. However, its role in hepatocellular carcinoma (HCC), one of the most prevalent human cancers worldwide, remains unclear. Here, we examined the involvement of ITGB4 in HCC and explored the underlying mechanisms. Real-time PCR and immunohistochemical analyses of tissues from 82 patients with HCC and four HCC cell lines showed higher ITGB4 levels in tumor than in adjacent non-tumor tissues and in HCC than in normal hepatic cells. Silencing of ITGB4 repressed cell proliferation, colony forming ability and cell invasiveness, whereas ectopic expression of ITGB4 promoted the proliferation and invasion of HCC cells and induced epithelial to mesenchymal transition (EMT) in parallel with the upregulation of Slug, as shown by transwell assays, WB and immunocytochemistry. Knockdown of Slug reduced cell viability inhibited invasion and reversed the effects of ITBG4 overexpression on promoting EMT, and AKT/Sox2-Nanog may also be involved. In a xenograft tumor model induced by injection of ITGB4-overexpressing cells into nude mice, ITGB4 promoted tumor growth and metastasis to the lungs. Taken together, our results indicate that ITGB4 plays a tumorigenic and pro-metastatic role mediated by Slug and suggest IGTB4 could be a prognostic indicator or a therapeutic target in patients with HCC.
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Educational Institute, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Xiao-Long
authors.initials: XL
authors.lastname: Li
authors.affiliation: Department of Interventional &Vascular Surgery, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Educational Institute, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Dan-Dan
authors.initials: DD
authors.lastname: Li
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Educational Institute, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: He
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Educational Institute, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Le-Hang
authors.initials: LH
authors.lastname: Guo
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Educational Institute, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Li-Ping
authors.initials: LP
authors.lastname: Sun
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Educational Institute, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Lin-Na
authors.initials: LN
authors.lastname: Liu
authors.affiliation: Department of Medical Ultrasound, Shanghai Tenth People's Hospital, Ultrasound Research and Educational Institute, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Hui-Xiong
authors.initials: HX
authors.lastname: Xu
authors.affiliation: Department of Interventional &Vascular Surgery, Tongji University School of Medicine, Shanghai 200072, China.
authors.forename: Xiao-Ping
authors.initials: XP
authors.lastname: Zhang
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D049109:Cell Proliferation / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D056945:Hep G2 Cells; D006801:Humans; D039663:Integrin beta4 / Q000378:metabolism*; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D008297:Male; D008819:Mice, Nude; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D000071250:Snail Family Transcription Factors / Q000378:metabolism*; D014410:Tumor Stem Cell Assay; D015854:Up-Regulation / Q000235:genetics
chemical_list: D039663:Integrin beta4; D000071250:Snail Family Transcription Factors