PIDDosome-induced p53-dependent ploidy restriction facilitates hepatocarcinogenesis

ABSTRACT: Polyploidization frequently precedes tumorigenesis but also occurs during normal development in several tissues. Hepatocyte ploidy is controlled by the PIDDosome during development and regeneration. This multi-protein complex is activated by supernumerary centrosomes to induce p53 and restrict proliferation of polyploid cells, otherwise prone for chromosomal instability. PIDDosome-deficiency in the liver results in drastically increased polyploidy. To investigate PIDDosome-induced p53-activation in the pathogenesis of liver cancer, we chemically induced hepatocellular carcinoma (HCC) in mice. Strikingly, PIDDosome-deficiency reduced tumor number and burden, despite the inability to activate p53 in polyploid cells. Liver tumors arise primarily from cells with low ploidy, indicating an intri

SUBMITTER: Dr. Valentina, C Sladky 

PROVIDER: S-SCDT-EMBOR-2020-50893-T | biostudies-other |

REPOSITORIES: biostudies-other