A Mouse Model of Cholangiocarcinoma Uncovers a Role for Tensin-4 in Tumor Progression.

Background And Aims: Earlier diagnosis and treatment of intrahepatic cholangiocarcinoma (iCCA) are necessary to improve therapy, yet limited information is available about initiation and evolution of iCCA precursor lesions. Therefore, there is a need to identify mechanisms driving formation of precancerous lesions and their progression toward invasive tumors using experimental models that faithfully recapitulate human tumorigenesis.

Approach And Results: To this end, we generated a mouse model which combines cholangiocyte-specific expression of Kras with 3,5-diethoxycarbonyl-1,4-dihydrocollidine (DDC) diet-induced inflammation to mimic iCCA development in patients with cholangitis.

Dynamics and predicted drug response of a gene network linking dedifferentiation with beta-catenin dysfunction in hepatocellular carcinoma.

Background & Aims: Alterations of individual genes variably affect the development of hepatocellular carcinoma (HCC). Thus, we aimed to characterize the function of tumor-promoting genes in the context of gene regulatory networks (GRNs).

Methods: Using data from The Cancer Genome Atlas, from the LIRI-JP (Liver Cancer - RIKEN, JP project), and from our transcriptomic, transfection and mouse transgenic experiments, we identify a GRN which functionally links LIN28B-dependent dedifferentiation with dysfunction of β-catenin (CTNNB1).