標題: Ribose-5-phosphate isomerase A overexpression promotes liver cancer development in transgenic zebrafish via activation of ERK and beta-catenin pathways
作者: Chou, Yu-Ting
Chen, Li-Yang
Tsai, Shin-Lin
Tu, Hsiao-Chen
Lu, Jeng-Wei
Ciou, Shih-Ci
Wang, Horng-Dar
Yuh, Chiou-Hwa
生物科技學系
Department of Biological Science and Technology
公開日期: 1-Mar-2019
摘要: 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 beta-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 beta-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.
URI: http://dx.doi.org/10.1093/carcin/bgy155
http://hdl.handle.net/11536/152214
ISSN: 0143-3334
DOI: 10.1093/carcin/bgy155
期刊: CARCINOGENESIS
Volume: 40
Issue: 3
起始頁: 461
結束頁: 473
Appears in Collections:Articles