DBF4 Dependent Kinase Inhibition Suppresses Hepatocellular Carcinoma Progression and Potentiates Anti-Programmed Cell Death-1 Therapy.

ABSTRACT: The progression of hepatocellular carcinoma (HCC) remains a huge clinical challenge, and elucidation of the underlying molecular mechanisms is critical to develop effective therapeutic strategy. Dumbbell former 4 (DBF4) complexes with cell division cycle 7 (CDC7) to form DBF4-dependent kinase (DDK), playing instrumental roles in tumor cell survival, whereas its roles in HCC remain elusive. This study revealed that DBF4 expression was upregulated in HCC and constituted an independent prognostic factor of patient survival. We identified p65 as an upstream inducer which increased DBF4 expression by directly binding to its promoter. DBF4 accelerated HCC cell proliferation and tumorigenesis in vitro and in vivo. Mechanistically, DBF4 complexed with CDC7 to bind to the coiled coil

SUBMITTER: Zhang L 

PROVIDER: S-EPMC10367558 | biostudies-literature | 2023

REPOSITORIES: biostudies-literature