Signal Transduction in Hepatocellular Carcinoma: Insights from Zebrafish

Abstract

The zebrafish has been an increasingly popular animal model for human diseases as it offers the combined advantages compared to various animal models and cell based assays; in particular, the feasibility of high throughput studies as an economical vertebrate model. In this past decade, we and several other laboratories have developed various hepatocellular carcinoma (HCC) models using the zebrafish and demonstrated the conservation of HCC between zebrafish and human at both histopathological and molecular levels. In this review, we focus on the conservation of signal transductions during hepatocarcinogenesis between zebrafish and human. Based on existing zebrafish HCC models, indeed many alterations of signal pathways that cause human liver cancers can also result in HCC in zebrafish, such as Ras pathway, EGFR pathway, Wng/β-catenin pathway, TGF-β pathway, PI3K/AKT pathway, JAK/STAT pathway, Hippo pathway, src tyrosine kinase pathway, etc. In future, zebrafish may be used for better quantification of signaling molecules and thus to aid development of more effective therapeutic methods.