title: Slug promotes hepatocellular cancer cell progression by increasing sox2 and nanog expression.
abstract: Transcription factor Slug plays an important role in the tumor invasion and metastasis of human hepatocellular carcinoma (HCC). This study aimed to explore the mechanism involved in the promotion of HCC progression by Slug. In the precent study, we demonstrated that Slug expression was significantly associated with metastasis and shorter survival time of HCC patients. Using ChIP-on-chip and microarray analysis, we identified the molecular profile of Slug downstream targets in HCC cells with Slug overexpression. The Wnt, Notch and Hedgehog pathways were identified to promote pluripotency maintaining overexpression factors sox2 and nanog. Importantly, Slug showed a close relationship with sox2 and nanog expression in HCC patients and in HCC xenografts in vivo. Notably, the DNA damaging reagent hydroxyurea had no effect on Slug, sox2 and nanog expression in HCC cells with Slug overexpression; however knockdown of Slug by the short hairpin RNA approach markedly reduced sox2 and nanog expression and inhibited HCC cell migration in vitro. The results of this study indicate that Slug promotes progression of HCC by promoting sox2 and nanog overexpression. The related molecular pathways may be used as novel therapeutic targets for HCC.
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Xiulan
authors.initials: X
authors.lastname: Zhao
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Baocun
authors.initials: B
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Dan
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Tieju
authors.initials: T
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Na
authors.initials: N
authors.lastname: Che
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Gu
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Xueyi
authors.initials: X
authors.lastname: Dong
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Rui
authors.initials: R
authors.lastname: Li
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Yanrong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Pathology, Tianjin Medical University, Tianjin 300052, P.R. China.
authors.forename: Jing
authors.initials: J
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis; D002465:Cell Movement; D018450:Disease Progression; D005260:Female; D015870:Gene Expression; D015972:Gene Expression Regulation, Neoplastic; D056945:Hep G2 Cells; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D008113:Liver Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology / Q000556:secondary; D008297:Male; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D008875:Middle Aged; D000071317:Nanog Homeobox Protein; D009368:Neoplasm Transplantation; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000502:physiology*
chemical_list: D018398:Homeodomain Proteins; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; C000604407:SNAI1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; C000604449:Snai2 protein, mouse; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors