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 HCC in vitro and in 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 HCC in vivo were 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 cells in vitro. The Slug overexpression group exhibited the highest rate of tumor growth compared with the Snail overexpression and control groups in 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.
Highlights
Detection of metastasis of hepatocellular carcinoma (HCC) is crucial for early diagnosis
The findings demonstrated a significant increase in CD133+ cells in the Slug overexpression group compared with the control group, but no significant difference was observed between the Snail overexpression and the control groups (Fig. 4)
HCC invasiveness is a key step that results in metastasis and a poor prognosis [1,11]; the underlying molecular mechanisms are a focus of investigation
Summary
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. The present study aimed to investigate whether Slug and Snail overexpression is associated with the invasiveness of HCC in vitro and in vivo. The Slug overexpression group exhibited the highest rate of tumor growth compared with the Snail overexpression and control groups in 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. A number of molecules associated with tumor invasion and EMT in HCC have been reported, including Twist, Snail and Slug [8,9,10]. The molecular changes associated with the metastatic ability in HCC progression have not been clearly determined
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