Please use this identifier to cite or link to this item: https://doi.org/10.18632/oncotarget.20357
Title: Chronically high level of tgfb1a induction causes both hepatocellular carcinoma and cholangiocarcinoma via a dominant Erk pathway in zebrafish
Authors: Yan, C 
Yang, Q 
Shen, H.-M 
Spitsbergen, J.M
Gong, Z 
Keywords: leptin
mitogen activated protein kinase
Smad protein
transforming growth factor beta1
adult
animal cell
animal experiment
animal model
animal tissue
Article
bile duct carcinoma
carcinogenesis
carcinogenicity
cholangiocyte
controlled study
disease course
gene induction
gene overexpression
hormone response
human
human tissue
larva
liver cell
liver cell carcinoma
long term exposure
MAPK signaling
molecular pathology
nonalcoholic fatty liver
nonhuman
oncogene
protein expression
satiety
tgfb1a gene
transgenic zebrafish
Issue Date: 2017
Citation: Yan, C, Yang, Q, Shen, H.-M, Spitsbergen, J.M, Gong, Z (2017). Chronically high level of tgfb1a induction causes both hepatocellular carcinoma and cholangiocarcinoma via a dominant Erk pathway in zebrafish. Oncotarget 8 (44) : 77096-77109. ScholarBank@NUS Repository. https://doi.org/10.18632/oncotarget.20357
Abstract: Liver cancers including both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) have increased steadily with the prevalence of nonalcoholic steatohepatitis (NASH), but the underlying mechanism for the transition from NASH to liver cancers remains unclear. Here we first employed diet-induced NASH zebrafish and found that elevated level of satiety hormone, leptin, induced overexpression of tgfb1. Then we developed tgfb1a transgenic zebrafish for inducible, hepatocyte-specific expression. Interestingly, chronically high tgfb1a induction in hepatocytes could concurrently drive both HCC and CCA. Molecularly, oncogenicity of Tgfb1 in HCC was dependent on the switch of dominant activated signaling pathway from Smad to Erk in hepatocytes while concurrent activation of both Smad and Erk pathways in cholangiocytes was essential for Tgfb1-induced CCA. These findings pinpointed the novel role of Tgfb1 as a central regulator in the two major types of liver cancers, which was also supported by human liver disease samples. © Yan et al.
Source Title: Oncotarget
URI: https://scholarbank.nus.edu.sg/handle/10635/173801
ISSN: 19492553
DOI: 10.18632/oncotarget.20357
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