title: Slug overexpression induces stemness and promotes hepatocellular carcinoma cell invasion and metastasis.
abstract: Detection of metastasis of hepatocellular carcinoma (HCC) is crucial for early diagnosis. Epithelial-mesenchymal transition (EMT) is a common event in the metastasis of tumor cells. Slug and Snail are homologous proteins, which play an important role in EMT. The present study aimed to investigate whether Slug and Snail overexpression is associated with the invasiveness of HCCin vitroandin vivo. Invasion, colony formation and wound healing assays, as well as flow cytometry analysis, were performed to examine the invasiveness and proliferation capabilities of HepG2 cells following transfection with cNDA or the siRNA of Slug or Snail. The effects of Slug on HCCin vivowere examined using a xenograft model. Slug upregulation increased the percentage of cluster of differentiation (CD)133+cells among HepG2 cells, and induced cell invasion and proliferation; whereas Snail upregulation did not affect the cellsin vitro. The Slug overexpression group exhibited the highest rate of tumor growth compared with the Snail overexpression and control groupsin vivo. These findings demonstrated that Slug increases the percentage of CD133+cells, promotes the clonigenicity of HCC cells and induces a stronger stemness in Slug-overexpressing cells. These changes activate dormant developmental pathways in invading tumor cells. Thus, Slug may serve as a novel target for HCC prognosis and therapy.
authors.affiliation: Department of Surgery, The Second Hospital of Tianjin Medical University, Hexi, Tianjin 300211, P.R. China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Surgery, The Second Hospital of Tianjin Medical University, Hexi, Tianjin 300211, P.R. China.
authors.forename: Guo-Dong
authors.initials: GD
authors.lastname: Song
authors.affiliation: Department of Surgery, The Second Hospital of Tianjin Medical University, Hexi, Tianjin 300211, P.R. China.
authors.forename: Ning
authors.initials: N
authors.lastname: Sun
authors.affiliation: Department of Surgery, The Second Hospital of Tianjin Medical University, Hexi, Tianjin 300211, P.R. China.
authors.forename: Jian-Qiu
authors.initials: JQ
authors.lastname: Chen
authors.affiliation: Department of Surgery, The Second Hospital of Tianjin Medical University, Hexi, Tianjin 300211, P.R. China.
authors.forename: Shao-Shi
authors.initials: SS
authors.lastname: Yang
keywords: Slug; epithelial-mesenchymal transition; hepatocellular carcinoma; stemness