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.
Highlights
To date, metastasis is still one of the main obstacles to the survival of patients with hepatocellular carcinoma (HCC) [1,2]
Real-time reverse transcription-PCR (RT-PCR) showed the upregulation of GSC in Hep3B cells, which was confirmed by the Western blot results (Figure 1C)
This study is the first to demonstrate that expression of the embryonic gene GSC is associated with the metastasis of HCC
Summary
Metastasis is still one of the main obstacles to the survival of patients with hepatocellular carcinoma (HCC) [1,2]. Collective cell migration is characterized as movement of groups of cells by membrane ruffling at the free edge only, while cell-cell junctions within the moving cell group remain intact. This process occurs in the developmental context during gastrulation [9] and formation of the neural crest [10]. Collective cell migration has been shown to play critical roles in invasion and spreading of tumors, such as melanoma. The essential genes that control EMT or collective cell migration during embryogenesis may potentially play critical roles in invasion and metastasis of malignancies
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