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: | 1-三月-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 |
顯示於類別: | 期刊論文 |