title: Goosecoid promotes the metastasis of hepatocellular carcinoma by modulating the epithelial-mesenchymal transition.
abstract: The homeobox gene, goosecoid (GSC), is a transcription factor that participates in cell migration during embryonic development. Because cell migration during development has characteristics similar to cell invasion during metastasis, we evaluated the potential role of GSC in the metastasis of hepatocellular carcinoma (HCC). GSC expression in HCC cell lines and tissues was evaluated, and its effects on the migration potential of HCC cells were determined by GSC knock-down and overexpression methods. In addition, the prognostic role of GSC expression in the metastasis of cancer cells in HCC patients was determined. Our data showed that GSC was highly expressed in several HCC cell lines, particularly in a highly metastatic HCC cell line. Overexpression of GSC promoted cell migration and invasion of HCC cells in vitro. Gain-of-function induced the epithelial-mesenchymal transition but not collective cell migration, whereas loss-of-function induced the reverse change. High-level expression of GSC correlated closely with poor survival and lung metastasis in HCC patients; lung metastases showed more upregulated GSC expression than the primary tumor. We conclude that GSC promotes metastasis of HCC potentially through initiating the epithelial-mesenchymal transition. GSC is also a prognostic factor for poor survival and metastasis of HCC, which suggests its potential as a therapeutic target for metastatic HCC.
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China.
authors.forename: Tong-Chun
authors.initials: TC
authors.lastname: Xue
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China.
authors.forename: Ning-Ling
authors.initials: NL
authors.lastname: Ge
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China.
authors.forename: Lan
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China.
authors.forename: Jie-Feng
authors.initials: JF
authors.lastname: Cui
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China.
authors.forename: Rong-Xin
authors.initials: RX
authors.lastname: Chen
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China.
authors.forename: Yang
authors.initials: Y
authors.lastname: You
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China.
authors.forename: Sheng-Long
authors.initials: SL
authors.lastname: Ye
authors.affiliation: Liver Cancer Institute, Zhongshan Hospital, Fudan University, Shanghai, P.R. China; Key Laboratory of Carcinogenesis and Cancer Invasion (Fudan University), Ministry of Education, Shanghai, P.R. China.
authors.forename: Zheng-Gang
authors.initials: ZG
authors.lastname: Ren
mesh_terms: D006528:Carcinoma, Hepatocellular / Q000235:genetics* / Q000473:pathology; D002465:Cell Movement; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics; D015972:Gene Expression Regulation, Neoplastic; D051956:Goosecoid Protein / Q000096:biosynthesis* / Q000235:genetics; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics* / Q000473:pathology; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000556:secondary; D009361:Neoplasm Invasiveness / Q000235:genetics*; D011379:Prognosis
chemical_list: C497992:GSC protein, human; D051956:Goosecoid Protein