PUBLICATION
RETRACTED: 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.
- ID
- ZDB-PUB-171105-7
- Date
- 2017
- Source
- Oncotarget 8: 77096-77109 (Journal)
- Registered Authors
- Keywords
- TGFb, cholangiocarcinoma (CCA), hepatocellular carcinoma (HCC), leptin, non-alcoholic steatohepatitis (NASH)
- MeSH Terms
- none
- PubMed
- 29100373 Full text @ Oncotarget
Citation
Yan, C., Yang, Q., Shen, H.M., Spitsbergen, J.M., Gong, Z. (2017) RETRACTED: Chronically high level of tgfb1a induction causes both hepatocellular carcinoma and cholangiocarcinoma via a dominant Erk pathway in zebrafish.. Oncotarget. 8:77096-77109.
Abstract
Liver cancers including both hepatocellular carcinoma (HCC) and cholangiocarcinoma (CCA) have increased steadily with the prevalence of non-alcoholic 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.
Errata / Notes
This article has retractions in ZDB-PUB-240515-1.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping