The portrait of liver cancer is shaped by mitochondrial genetics.

ABSTRACT: Cancer heterogeneity and evolution are not fully understood. Here, we show that mitochondrial DNA of the normal liver shapes tumor progression, histology, and immune environment prior to the acquisition of oncogenic mutation. Using conplastic mice, we show that mtDNA dictates the expression of the mitochondrial unfolded protein response (UPR^mt) in the normal liver. Activation of oncogenic mutations in UPR^mt-positive liver increases tumor incidence and histological heterogeneity. Further, in a subset of UPR^mt-positive mice, invasive liver cancers develop. RNA sequencing (RNA-seq) analysis of the normal liver reveals that, in this subset, the PAPP-A/DDR2/SNAIL axis of invasion pre-exists along with elevated collagen. Since PAPP-A promotes immune evasion, we a

SUBMITTER: Chattopadhyay M 

PROVIDER: S-EPMC8808357 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature