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Title: Chemical inhibition reveals differential requirements of signaling pathways in krasV12-and Myc-induced liver tumors in transgenic zebrafish
Authors: Yan, C 
Yang, Q 
Huo, X 
Li, H
Zhou, L 
Gong, Z 
Keywords: fibroblast growth factor
Kras protein, zebrafish
protein p21
vasculotropin A
zebrafish protein
antagonists and inhibitors
disease model
experimental liver neoplasm
liver cell carcinoma
liver tumor
oncogene myc
signal transduction
transgenic animal
zebra fish
Animals, Genetically Modified
Carcinoma, Hepatocellular
Disease Models, Animal
Fibroblast Growth Factors
Genes, myc
Liver Neoplasms
Liver Neoplasms, Experimental
Proto-Oncogene Proteins p21(ras)
Signal Transduction
Vascular Endothelial Growth Factor A
Zebrafish Proteins
Issue Date: 2017
Publisher: Nature Publishing Group
Citation: Yan, C, Yang, Q, Huo, X, Li, H, Zhou, L, Gong, Z (2017). Chemical inhibition reveals differential requirements of signaling pathways in krasV12-and Myc-induced liver tumors in transgenic zebrafish. Scientific Reports 7 : 45796. ScholarBank@NUS Repository.
Abstract: Previously we have generated inducible liver tumor models by transgenic expression of an oncogene and robust tumorigenesis can be rapidly induced by activation of the oncogene in both juvenile and adult fish. In the present study, we aimed at chemical intervention of tumorigenesis for understanding molecular pathways of tumorigenesis and for potential development of a chemical screening tool for anti-cancer drug discovery. Thus, we evaluated the roles of several major signaling pathways in krasV12-or Myc-induced liver tumors by using several small molecule inhibitors: SU5402 and SU6668 for VEGF/FGF signaling; IWR1 and cardionogen 1 for Wnt signaling; and cyclopamine and Gant61 for Hedgehog signaling. Inhibition of VEGF/FGF signaling was found to deter both Myc-and krasV12-induced liver tumorigenesis while suppression of Wnt signaling relaxed only Myc-but not krasV12-induced liver tumorigenesis. Inhibiting Hedgehog signaling did not suppress either krasV12 or Myc-induced tumors. The suppression of liver tumorigenesis was accompanied with a decrease of cell proliferation, increase of apoptosis, distorted liver histology. Collectively, our observations suggested the requirement of VEGF/FGF signaling but not the hedgehog signaling in liver tumorigenesis in both transgenic fry. However, Wnt signaling appeared to be required for liver tumorigenesis only in Myc but not krasV12 transgenic zebrafish. © 2017 The Author(s).
Source Title: Scientific Reports
ISSN: 2045-2322
DOI: 10.1038/srep45796
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