2024-03-28T15:50:05Zhttp://repisalud.isciii.es/oai/requestoai:repisalud.isciii.es:20.500.12105/156662023-04-26T14:48:17Zcom_20.500.12105_2145com_20.500.12105_2051com_20.500.12105_2144col_20.500.12105_2146
00925njm 22002777a 4500
dc
Chattopadhyay, Mrittika
author
Jenkins, Edmund Charles
author
Lechuga-Vieco, Ana Victoria
author
Nie, Kai
author
Fiel, Maria Isabel
author
Rialdi, Alexander
author
Guccione, Ernesto
author
Enriquez, Jose Antonio
author
Sia, Daniela
author
Lujambio, Amaia
author
Germain, Doris
author
2022-01-18
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 (UPRmt) in the normal liver. Activation of oncogenic mutations in UPRmt-positive liver increases tumor incidence and histological heterogeneity. Further, in a subset of UPRmt-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 analyzed the immune signature and found that their livers are immunosuppressed. Further, the PAPP-A signature identifies the immune exhausted subset of hepatocellular carcinoma (HCC) in humans. Our data suggest that mtDNA of normal liver shapes the entire liver cancer portrait upon acquisition of oncogenic mutations.
Cell Rep. 2022 Jan 18;38(3):110254
http://hdl.handle.net/20.500.12105/15666
35045282
10.1016/j.celrep.2021.110254
2211-1247
Cell reports
The portrait of liver cancer is shaped by mitochondrial genetics.