PUBLICATION
Notch-Sox9 Axis Mediates Hepatocyte Dedifferentiation in KrasG12V-Induced Zebrafish Hepatocellular Carcinoma
- Authors
- Sun, J., Chen, Q., Ma, J.
- ID
- ZDB-PUB-220515-6
- Date
- 2022
- Source
- International Journal of Molecular Sciences 23(9): (Journal)
- Registered Authors
- Ma, Jianlong
- Keywords
- Notch, Sox9, cancer model, dedifferentiation, hepatocellular carcinoma
- MeSH Terms
-
- Animals
- Carcinogenesis/metabolism
- Carcinoma, Hepatocellular*/metabolism
- Hepatocytes/metabolism
- Liver Neoplasms*/metabolism
- Proto-Oncogene Proteins p21(ras)/metabolism
- Zebrafish/genetics
- Zebrafish/metabolism
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 35563098 Full text @ Int. J. Mol. Sci.
Citation
Sun, J., Chen, Q., Ma, J. (2022) Notch-Sox9 Axis Mediates Hepatocyte Dedifferentiation in KrasG12V-Induced Zebrafish Hepatocellular Carcinoma. International Journal of Molecular Sciences. 23(9):.
Abstract
Liver cancer is one of the most prevalent cancers in humans. Hepatocytes normally undergo dedifferentiation after the onset of hepatocellular carcinoma, which in turn facilitates the progression of cancer. Although the process of hepatocellular carcinoma dedifferentiation is of significant research and clinical value, the cellular and molecular mechanisms underlying it are still not fully characterized. We constructed a zebrafish liver cancer model based on overexpression of the oncogene krasG12V to investigate the hepatocyte dedifferentiation in hepatocellular carcinoma. We found that, after hepatocarcinogenesis, hepatocytes dedifferentiated and the Notch signaling pathway was upregulated in this progress. Furthermore, we found that inhibition of the Notch signaling pathway or deficiency of sox9b both prevented hepatocyte dedifferentiation following hepatocellular carcinoma induction, reducing cancer metastasis and improving survival. In conclusion, we found that hepatocytes undergo dedifferentiation after hepatocarcinogenesis, a process that requires Notch signaling and likewise the activation of Sox9.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping