DNAJ-PKAc fusion heightens PLK1 inhibitor sensitivity in fibrolamellar carcinoma.

ABSTRACT:

Background

Fibrolamellar carcinoma (FLC), a rare and fatal liver cancer lacking effective drug therapy, is driven by the DNAJ-PKAc fusion oncoprotein. However, the underlying mechanism of DNAJ-PKAc's role in FLC tumour growth remains enigmatic.

Objective

We sought to determine the protein kinase-mediated signalling networks that drive growth and proliferation in FLC.

Design

We integrated a combination of newly established preclinical models of FLC and an unbiased polypharmacology-based approach to identify downstream kinases involved in DNAJ-PKAc-mediated FLC cell growth. We validated our findings in multiple patient-derived mouse models and patient tumours.

Results

Functional screening, coupled with computational analysis, highlighted Polo-like kinase 1 (PLK1)

SUBMITTER: Chan M 

PROVIDER: S-EPMC12505043 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature