Exacerbation of Liver Tumor Metastasis in <i>twist1a+</i>/<i>xmrk+</i> Double Transgenic Zebrafish following Lipopolysaccharide or Dextran Sulphate Sodium Exposure
The poor prognosis for patients with hepatocellular carcinoma (HCC) is related directly to metastasis. The <i>T</i><i>wist1</i> gene encodes for a transcription factor essential to embryogenesis. It has also been shown to promote epithelial-to-mesenchymal transition (EMT), in...
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| Main Authors: | , , , , |
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| Format: | Book |
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MDPI AG,
2021-08-01T00:00:00Z.
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| Summary: | The poor prognosis for patients with hepatocellular carcinoma (HCC) is related directly to metastasis. The <i>T</i><i>wist1</i> gene encodes for a transcription factor essential to embryogenesis. It has also been shown to promote epithelial-to-mesenchymal transition (EMT), invasion, and metastasis; however, there is currently no in vivo evidence that <i>Twist1</i> plays a role in the metastasis of liver tumors. Zebrafish are increasingly being used as an alternative cancer model. In the current study, an adult-stage zebrafish HCC model was used to examine the synergistic effects of <i>twist1a</i> and <i>xmrk</i>, a well characterized oncogene, during HCC metastasis. We also examined the effects of two inflammatory agents, lipopolysaccharides (LPS) and dextran sulfate sodium (DSS), on the hepatocyte-specific expression of transgenic <i>twist1a</i> and <i>xmrk</i>. The conditional overexpression of <i>twist1a</i> and <i>xmrk</i> was shown to promote liver tumor metastasis in zebrafish, resulting in increased apoptosis and cell proliferation as well as tumor maintenance and propagation independent of the inherent EMT-inducing activity of <i>xmrk</i>. Exposing <i>twist1a+</i>/<i>xmrk+</i> transgenic zebrafish to LPS or DSS was shown to promote metastasis, indicating that the overexpression of <i>twist1a</i> and <i>xmrk</i> led to crosstalk between the signaling pathways involved in EMT. This study provides important evidence pertaining to the largely overlooked effects of signaling crosstalk between <i>twist1a</i> and <i>xmrk</i> in regulating HCC metastasis. Our results also suggest that the co-expression of <i>twist1a</i>/<i>xmrk</i> in conjunction with exposure to LPS or DSS enhances HCC metastasis, and provides a valuable in vivo platform by which to investigate tumor initiation and metastasis in the study of liver cancer. |
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| Item Description: | 10.3390/ph14090867 1424-8247 |