Show simple item record

dc.contributor.authorChattopadhyay, Mrittika
dc.contributor.authorJenkins, Edmund Charles
dc.contributor.authorLechuga-Vieco, Ana Victoria
dc.contributor.authorNie, Kai
dc.contributor.authorFiel, Maria Isabel
dc.contributor.authorRialdi, Alexander
dc.contributor.authorGuccione, Ernesto
dc.contributor.authorEnriquez, Jose Antonio 
dc.contributor.authorSia, Daniela
dc.contributor.authorLujambio, Amaia
dc.contributor.authorGermain, Doris
dc.identifier.citationCell Rep. 2022 Jan 18;38(3):110254es_ES
dc.description.abstractCancer 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.es_ES
dc.description.sponsorshipThis work was supported by an RO1 AG059635 award from the NIH to D.G.es_ES
dc.publisherCell Press es_ES
dc.subject.meshAnimals es_ES
dc.subject.meshCarcinoma, Hepatocellular es_ES
dc.subject.meshDNA, Mitochondrial es_ES
dc.subject.meshFemale es_ES
dc.subject.meshHumans es_ES
dc.subject.meshLiver Neoplasms es_ES
dc.subject.meshMale es_ES
dc.subject.meshMice es_ES
dc.subject.meshMice, Inbred C57BL es_ES
dc.subject.meshPregnancy-Associated Plasma Protein-A es_ES
dc.subject.meshTranscriptome es_ES
dc.subject.meshUnfolded Protein Response es_ES
dc.titleThe portrait of liver cancer is shaped by mitochondrial genetics.es_ES
dc.typejournal articlees_ES
dc.rights.licenseAttribution-NonCommercial-NoDerivatives 4.0 Internacional*
dc.identifier.journalCell reportses_ES
dc.repisalud.orgCNICCNIC::Grupos de investigación::Genética Funcional del Sistema de Fosforilación Oxidativaes_ES
dc.rights.accessRightsopen accesses_ES

Files in this item

Acceso Abierto

This item appears in the following Collection(s)

Show simple item record

Attribution-NonCommercial-NoDerivatives 4.0 Internacional
This item is licensed under a: Attribution-NonCommercial-NoDerivatives 4.0 Internacional