Ribose-5-phosphate isomerase A overexpression promotes liver cancer development in transgenic zebrafish via activation of ERK and ß-catenin pathways.
Carcinogenesis
; 40(3): 461-473, 2019 05 14.
Article
in En
| MEDLINE
| ID: mdl-30418535
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 ß-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 ß-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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Aldose-Ketose Isomerases
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Extracellular Signal-Regulated MAP Kinases
/
Beta Catenin
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Liver Neoplasms, Experimental
Limits:
Animals
Language:
En
Journal:
Carcinogenesis
Year:
2019
Document type:
Article