Identification of Chemical Inhibitors of β-Catenin-Driven Liver Tumorigenesis in Zebrafish

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Liver cancer is a leading cause of cancer-related death. Genetic analysis of liver cancer has enabled classification of these tumors into subsets with unique genetic, clinical, and prognostic features. The search for targeted liver cancer treatments has been hampered by the lack of relevant animal models for these genetically diverse subsets, including liver cancers that are defined by activating mutations in the gene encoding β-catenin, an integral component of the Wnt signaling pathway. Here we describe the generation and characterization of genetically modified zebrafish expressing hepatocyte-specific activated β-catenin. We used this new zebrafish model to screen for drugs that suppress β-catenin-induced liver growth, and identified two classes of hits, c-Jun N-terminal kinase (JNK) inhibitors and antidepressants, that suppressed this phenotype. Our findings provide insights into the mechanisms by which β-catenin promotes liver tumor formation and implicate JNK inhibitors and antidepressants as potential treatments for a subset of human liver cancers.

Vyšlo v časopise: Identification of Chemical Inhibitors of β-Catenin-Driven Liver Tumorigenesis in Zebrafish. PLoS Genet 11(7): e32767. doi:10.1371/journal.pgen.1005305
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1005305

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