|ZFIN ID: ZDB-PUB-181114-19|
Ribose-5-Phosphate Isomerase A Overexpression Promotes Liver Cancer Development in Transgenic Zebrafish via Activation of ERK and β-catenin Pathways
Chou, Y.T., Chen, L.Y., Tsai, S.L., Tu, H.C., Lu, J.W., Ciou, S.C., Wang, H.D., Yuh, C.H.
|Source:||Carcinogenesis 40(3): 461-473 (Journal)|
|Registered Authors:||Lu, Jeng-Wei, Tu, Hsiao-Chen, Yuh, Chiou-Hwa (Cathy)|
|PubMed:||30418535 Full text @ Carcinogenesis|
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.
ABSTRACTDysregulation 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.