Mitochondrial fitness and cancer risk
Kossenkov AV, Milcarek A, Notta F, Jang GH, Wilson JM, Gallinger S, Zhou DC, Ding L, Ghosh JC, Perego M, Morotti A, Locatelli M, Robert ME, Vaira V, Altieri DC. Mitochondrial fitness and cancer risk. PLOS ONE 2022, 17: e0273520. PMID: 36223343, PMCID: PMC9555630, DOI: 10.1371/journal.pone.0273520.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaSenescence-Associated Secretory PhenotypeIndependent patient cohortsPoor patient outcomesAggressive disease variantFolfirinox failureLocal inflammationPatient cohortDuctal adenocarcinomaPatient outcomesPatient riskMultiple malignanciesCancer riskMitochondrial fitnessSecretory phenotypeGene signatureHallmarks of cancerMetastatic propensityNormal tissuesHuman tumorsInterferon SignalingTumorsInner membrane mitochondrial proteinMalignancyMolecular signaturesGhost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability
Ghosh JC, Perego M, Agarwal E, Bertolini I, Wang Y, Goldman AR, Tang HY, Kossenkov AV, Landis CJ, Languino LR, Plow EF, Morotti A, Ottobrini L, Locatelli M, Speicher DW, Caino MC, Cassel J, Salvino JM, Robert ME, Vaira V, Altieri DC. Ghost mitochondria drive metastasis through adaptive GCN2/Akt therapeutic vulnerability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2022, 119: e2115624119. PMID: 35177476, PMCID: PMC8872753, DOI: 10.1073/pnas.2115624119.Peer-Reviewed Original ResearchMeSH KeywordsCell DeathCell Line, TumorCell MovementCell ProliferationEpithelial-Mesenchymal TransitionHumansMitochondriaMitochondrial DynamicsMitochondrial ProteinsMuscle ProteinsNeoplasm InvasivenessNeoplasm MetastasisNeoplasmsNeoplastic ProcessesProtein Serine-Threonine KinasesProto-Oncogene Proteins c-aktReactive Oxygen SpeciesSignal TransductionConceptsEpithelial-mesenchymal transitionGene expression programsTherapeutic vulnerabilitiesTumor cell movementCytokine/chemokine signalingExpression programsTherapeutic targetCell movementMitochondrial dynamicsEssential scaffoldMitochondrial structureSurvival signalingMitochondrial integrityCancer metabolismStress responseActionable therapeutic targetsCell deathChemokine signalingMitochondriaSmall-molecule drug screensCell proliferationOxidative damageInnate immunityMetastatic disseminationHuman tumors