The purpose of this study was to examine the role of human genomic regions, called cancer-enhancing genomic regions or aggressive liver cancer domains (CEGRs/ALCDs), in the development of FLC. In previous investigations of the mutation-independent pathways of pediatric liver cancer hepatoblastoma, researchers identified CEGRs/ALCDs that control the expression of a group of cancer-causing genes.
In FLC, the study determined that the fusion protein DNAJB1-PKAc activates a pathway involving a protein called β-catenin. This pathway leads to the activation of certain genes, including SPARC, which is known to cause fibrosis (scarring) in the liver.
To investigate these pathways further, the researchers used a drug called PRI-724 to inhibit β-catenin. They found that inhibiting β-catenin reduced the expression of CEGR/ALCD-containing genes and inhibited the growth of FLC.
In summary, the study suggests that the DNAJB1-PKAc-β-catenin-TCF4-CEGR/ALCD pathway is a key driver of fibrosis in FLC. In addition, it suggests that inhibiting β-catenin could be a potential therapy for FLC and could potentially help prevent its spread to other parts of the body.
Note: This study was partially funded by FCF.