2022
Ghost 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
2021
Trefoil factor 2 secreted from damaged hepatocytes activates hepatic stellate cells to induce fibrogenesis
Zhang B, Lapenta K, Wang Q, Nam JH, Chung D, Robert ME, Nathanson MH, Yang X. Trefoil factor 2 secreted from damaged hepatocytes activates hepatic stellate cells to induce fibrogenesis. Journal Of Biological Chemistry 2021, 297: 100887. PMID: 34146542, PMCID: PMC8267550, DOI: 10.1016/j.jbc.2021.100887.Peer-Reviewed Original ResearchConceptsHepatic stellate cellsTrefoil factor 2Liver injuryStellate cellsActivation of HSCsPrimary hepatic stellate cellsPlatelet-derived growth factor receptor betaChronic liver diseaseGrowth factor receptor betaProcess of fibrogenesisLiver-specific deletionFactor 2Spontaneous fibrosisLiver diseaseLiver fibrosisFibrogenic processReceptor betaFibrogenesisWT hepatocytesProtein expressionFibrosisHepatocytesInjuryNovel factorActivation
2020
OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance
Yang Y, Li X, Luan HH, Zhang B, Zhang K, Nam JH, Li Z, Fu M, Munk A, Zhang D, Wang S, Liu Y, Albuquerque JP, Ong Q, Li R, Wang Q, Robert ME, Perry RJ, Chung D, Shulman GI, Yang X. OGT suppresses S6K1-mediated macrophage inflammation and metabolic disturbance. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 16616-16625. PMID: 32601203, PMCID: PMC7368321, DOI: 10.1073/pnas.1916121117.Peer-Reviewed Original ResearchConceptsRibosomal protein S6 kinase beta-1Macrophage proinflammatory activationGlcNAc signalingProinflammatory activationUnexpected roleWhole-body metabolismNutrient fluxesLipid accumulationImmune cell activationGlcNAcHomeostatic mechanismsMetabolic disturbancesBeta 1Cell activationDiet-induced metabolic dysfunctionDiet-induced obese miceActivationWhole-body insulin resistanceMacrophage inflammationGlcNAcylationOGTPeripheral tissuesPhosphorylationEnhanced inflammationInsulin resistance