PUBLICATION
Ribose-5-Phosphate Isomerase A Overexpression Promotes Liver Cancer Development in Transgenic Zebrafish via Activation of ERK and β-catenin Pathways
- Authors
- Chou, Y.T., Chen, L.Y., Tsai, S.L., Tu, H.C., Lu, J.W., Ciou, S.C., Wang, H.D., Yuh, C.H.
- ID
- ZDB-PUB-181114-19
- Date
- 2018
- Source
- Carcinogenesis 40(3): 461-473 (Journal)
- Registered Authors
- Lu, Jeng-Wei, Tu, Hsiao-Chen, Yuh, Chiou-Hwa (Cathy)
- Keywords
- none
- MeSH Terms
-
- Aldose-Ketose Isomerases/metabolism*
- Animals
- Animals, Genetically Modified
- Cell Line, Tumor
- Disease Progression
- Extracellular Signal-Regulated MAP Kinases/metabolism*
- Liver Neoplasms, Experimental/enzymology
- Liver Neoplasms, Experimental/metabolism
- Liver Neoplasms, Experimental/pathology*
- Zebrafish/genetics
- beta Catenin/metabolism*
- PubMed
- 30418535 Full text @ Carcinogenesis
Citation
Chou, Y.T., Chen, L.Y., Tsai, S.L., Tu, H.C., Lu, J.W., Ciou, S.C., Wang, H.D., Yuh, C.H. (2018) Ribose-5-Phosphate Isomerase A Overexpression Promotes Liver Cancer Development in Transgenic Zebrafish via Activation of ERK and β-catenin Pathways. Carcinogenesis. 40(3):461-473.
Abstract
Dysregulation of the enzymes involved in the pentose phosphate pathway (PPP) is known to promote tumorigenesis. Our recent study demonstrated that ribose-5-phosphate isomerase (RPIA), a key regulator of the PPP, regulates hepatoma cell proliferation and colony formation. Our studies in zebrafish reveal that RPIA-mediated hepatocarcinogenesis requires extracellular signal-regulated kinase (ERK) and β-catenin signaling. To further investigate RPIA-mediated hepatocarcinogenesis, two independent lines of transgenic zebrafish expressing human RPIA in the liver were generated. These studies reveal that RPIA overexpression triggers lipogenic factor/enzyme expression, steatosis, fibrosis and proliferation of the liver. In addition, the severity of fibrosis and the extent of proliferation are positively correlated with RPIA expression levels. Furthermore, RPIA-mediated induction of hepatocellular carcinoma (HCC) requires the ERK and β-catenin signaling pathway but is not dependent upon transaldolase levels. Our study presents a mechanism for RPIA-mediated hepatocarcinogenesis and suggests that RPIA represents a valuable therapeutic target for the treatment of HCC.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping