Hepatocyte ploidy modulation in liver cancer

Abstract

Polyploidy, a balanced amplification of the genome, is common in the liver. The function of hepatic polyploidy is not entirely clear, but growing evidence shows that polyploidy can protect the liver from tumor formation. In this issue of EMBO Reports, Sladky and colleagues identify the PIDDosome as a polyploidy sensor that regulates liver cancer (Sladky et al, 2020b).

Figure 1. PIDDosome pathway regulates HCC initiation and expansion

(A) PIDDosome activity promotes controlled hepatocyte polyploidization, producing a “normal” ploidy spectrum that is sensitive to tumorigenesis. The ratio of each ploidy population is indicated for mice. The absence of PIDDosome leads to unrestrained polyploidization and hyperpolyploidy, which contributes to tumor resistance. (B) Tumor initiation (asterisks) occurs primarily in lower‐ploidy hepatocytes (mostly 2n and possibly 4n), and once transformed, they acquire proliferation signatures that drive expansion