2022
Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells.
McBrearty N, Cho C, Chen J, Zahedi F, Peck A, Radaelli E, Assenmacher C, Pavlak C, Devine A, Yu P, Lu Z, Zhang H, Li J, Pitarresi J, Astsaturov I, Cukierman E, Rustgi A, Stanger B, Rui H, Fuchs S. Tumor-Suppressive and Immune-Stimulating Roles of Cholesterol 25-hydroxylase in Pancreatic Cancer Cells. Molecular Cancer Research 2022, 21: 228-239. PMID: 36378658, PMCID: PMC9992122, DOI: 10.1158/1541-7786.mcr-22-0602.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaPancreatic cancer cellsPDAC cellsCH25H expressionTumor growthT cell tumor infiltrationMouse PDAC cellsImmune checkpoint inhibitorsCancer cellsDownregulation of MHCPancreatic intraepithelial neoplasiaImmune-competent hostsHuman pancreatic cancerPotential translational importanceAccumulation of cholesterolCheckpoint inhibitorsIntraepithelial neoplasiaPoor prognosisTumor infiltrationPancreatic cancerDuctal adenocarcinomaTherapeutic approachesCH25HTumor progressionCholesterol deficitInduction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities
Lu Z, Bae E, Verginadis I, Zhang H, Cho C, McBrearty N, George S, Diehl J, Koumenis C, Bradley L, Fuchs S. Induction of the activating transcription factor-4 in the intratumoral CD8+ T cells sustains their viability and anti-tumor activities. Cancer Immunology, Immunotherapy 2022, 72: 815-826. PMID: 36063172, PMCID: PMC10317204, DOI: 10.1007/s00262-022-03286-2.Peer-Reviewed Original ResearchConceptsActivity of CD8Tumor-derived factorsT cellsTumor microenvironmentTranscription factor 4Anti-tumor immunityImmune suppressive factorsFactor 4Anti-tumor activityFunction of ATF4Anti-cancer therapyIntratumoral CD8Cytotoxic CD8Immune therapyTherapeutic regimensAntigenic stimulationCD8Suppressive factorsT lymphocytesMouse modelImpaired activationWild-type counterpartsSelective ablationTherapyInduction of ATF4Could Programmed Death-Ligand 1 Copy Number Alterations be a Predictive Biomarker for Immunotherapy Response?
Woodard GA, Cho C, Chen L. Could Programmed Death-Ligand 1 Copy Number Alterations be a Predictive Biomarker for Immunotherapy Response? Journal Of Thoracic Oncology 2022, 17: 592-595. PMID: 35465963, DOI: 10.1016/j.jtho.2022.03.009.Peer-Reviewed Original ResearchAblation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy
Hu L, Chen L, Xiao Z, Zheng X, Chen Y, Xian N, Cho C, Luo L, Huang G, Chen L. Ablation of T cell-associated PD-1H enhances functionality and promotes adoptive immunotherapy. JCI Insight 2022, 7: e148247. PMID: 34905507, PMCID: PMC8855794, DOI: 10.1172/jci.insight.148247.Peer-Reviewed Original ResearchConceptsPD-1HT cellsAdoptive immunotherapyT cell-mediated immune responsesT-cell adoptive immunotherapyAdoptive T-cell therapyCell-mediated immune responsesTumor-infiltrating CD8Antitumor activityT-cell therapySyngeneic mouse tumorsCAR T cellsDeath-1 homologExperimental tumor modelsAdoptive transferActivated CD8Coinhibitory moleculesCytokine productionDeficient miceImmune responseHuman xenograftsCD8Tumor microenvironmentTumor modelMouse tumors
2021
Regulation of intercellular biomolecule transfer–driven tumor angiogenesis and responses to anticancer therapies
Lu Z, Ortiz A, Verginadis I, Peck A, Zahedi F, Cho C, Yu P, DeRita R, Zhang H, Kubanoff R, Sun Y, Yaspan A, Krespan E, Beiting D, Radaelli E, Ryeom S, Diehl J, Rui H, Koumenis C, Fuchs S. Regulation of intercellular biomolecule transfer–driven tumor angiogenesis and responses to anticancer therapies. Journal Of Clinical Investigation 2021, 131: e144225. PMID: 33998600, PMCID: PMC8121529, DOI: 10.1172/jci144225.Peer-Reviewed Original ResearchConceptsTumor growthEndothelial cellsMetastatic diseaseAnticancer therapyPoor disease outcomeColorectal cancerIntratumoral angiogenesisAngiostatic effectsDisease outcomeTherapeutic effectSide effectsOverall efficacyPharmacologic inhibitionTumor angiogenesisCH25HTherapyBenign cellsAngiogenesisDiseaseLow levelsCellsRegimensPatientsReserpineCancer
2020
Cancer-associated fibroblasts downregulate type I interferon receptor to stimulate intratumoral stromagenesis
Cho C, Mukherjee R, Peck AR, Sun Y, McBrearty N, Katlinski KV, Gui J, Govindaraju PK, Puré E, Rui H, Fuchs SY. Cancer-associated fibroblasts downregulate type I interferon receptor to stimulate intratumoral stromagenesis. Oncogene 2020, 39: 6129-6137. PMID: 32807917, PMCID: PMC7502515, DOI: 10.1038/s41388-020-01424-7.Peer-Reviewed Original ResearchConceptsCancer-associated fibroblastsFibroblast activation proteinType I interferon receptorTumor growthPancreatic ductal adenocarcinoma tumorsInterferon receptorKnockdown of Smad7Human colorectal cancerGrowth of tumorsSA miceColorectal cancerAdenocarcinoma tumorsSolid tumorsIFNAR1 downregulationGenetic ablationTumorsActivation proteinElevated levelsExtracellular matrixInverse correlationMiceStromagenesisIFNAR1IFNAR1 chainFAP levelsActivation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs
Gui J, Zahedi F, Ortiz A, Cho C, Katlinski K, Alicea-Torres K, Li J, Todd L, Zhang H, Beiting D, Sander C, Kirkwood J, Snow B, Wakeham A, Mak T, Diehl J, Koumenis C, Ryeom S, Stanger B, Puré E, Gabrilovich D, Fuchs S. Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs. Nature Cancer 2020, 1: 603-619. PMID: 34124690, PMCID: PMC8194112, DOI: 10.1038/s43018-020-0064-0.Peer-Reviewed Original ResearchConceptsPre-metastatic nicheFibroblast activation proteinStress-activated protein kinasePrimary tumor-derived factorsActivation proteinDisseminated malignant cellsNormal cellsActivity of p38Tumor-derived factorsExpression of chemokinesActivation of p38αInactivation of p38Subsequent pulmonary metastasesStimulation of expressionType I interferonProtein kinaseLung infiltrationP38 inhibitorAdjuvant therapyMetastatic diseaseP38α kinasePulmonary metastasesLung metastasesPoor prognosisMetastatic cancerFibronectin in the Tumor Microenvironment Activates a TLR4-dependent Inflammatory Response in Lung Cancer Cells
Cho C, Horzempa C, Longo CM, Peters DM, Jones DM, McKeown-Longo PJ. Fibronectin in the Tumor Microenvironment Activates a TLR4-dependent Inflammatory Response in Lung Cancer Cells. Journal Of Cancer 2020, 11: 3099-3105. PMID: 32231714, PMCID: PMC7097952, DOI: 10.7150/jca.39771.Peer-Reviewed Original ResearchType III domainExtracellular matrixLung cancer cellsFibronectin type III domainTumor-associated extracellular matrixCancer cellsFibronectin-rich extracellular matrixTLR4-dependent inflammatory responsesRich extracellular matrixFirst Type III domainIL-8Secondary structureStrained conformationMatrix fibronectinNF-κB pathwayEssential roleFibrotic microenvironmentTumor metastasisPathwayConformational labilityStromal cellsTumor progressionCytokine releaseLung cancerInflammatory responseActivation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs
Gui J, Zahedi F, Ortiz A, Cho C, Katlinski K V, Alicea-Torres K et al. Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs. Nat Cancer 2020; 1: 603–619Peer-Reviewed Original Research
2019
An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles
Ortiz A, Gui J, Zahedi F, Yu P, Cho C, Bhattacharya S, Carbone CJ, Yu Q, Katlinski KV, Katlinskaya YV, Handa S, Haas V, Volk SW, Brice AK, Wals K, Matheson NJ, Antrobus R, Ludwig S, Whiteside TL, Sander C, Tarhini AA, Kirkwood JM, Lehner PJ, Guo W, Rui H, Minn AJ, Koumenis C, Diehl JA, Fuchs SY. An Interferon-Driven Oxysterol-Based Defense against Tumor-Derived Extracellular Vesicles. Cancer Cell 2019, 35: 33-45.e6. PMID: 30645975, PMCID: PMC6336114, DOI: 10.1016/j.ccell.2018.12.001.Peer-Reviewed Original ResearchConceptsTumor-derived extracellular vesiclesMelanoma lung metastasisPre-metastatic nicheLung metastasesAdjuvant melanoma therapyAnti-hypertensive drugsUse of reserpineExtracellular vesiclesType I interferon receptorMelanoma patientsPoor prognosisCH25HMelanoma therapyIFN receptorInterferon receptorMetastasisNormal cellsHealthy cellsReceptorsUptakeCellsPatientsPrognosisReserpineTherapy
2016
The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells
Cho C, Horzempa C, Jones D, McKeown-Longo PJ. The fibronectin III-1 domain activates a PI3-Kinase/Akt signaling pathway leading to αvβ5 integrin activation and TRAIL resistance in human lung cancer cells. BMC Cancer 2016, 16: 574. PMID: 27484721, PMCID: PMC4970220, DOI: 10.1186/s12885-016-2621-6.Peer-Reviewed Original ResearchMeSH KeywordsCarcinoma, Non-Small-Cell LungCaspase 8Cell Line, TumorCell SurvivalDrug Resistance, NeoplasmFibronectin Type III DomainFibronectinsGene Expression Regulation, NeoplasticHumansLung NeoplasmsPhosphatidylinositol 3-KinasesProtein FoldingProto-Oncogene Proteins c-aktReceptors, VitronectinSignal TransductionTNF-Related Apoptosis-Inducing LigandVitronectinConceptsType III domainLung cancer cellsUnfolded domainsTRAIL resistancePI3-kinase/AktSerine/threonine kinase pathwaysCancer cellsMulti-modular proteinThreonine kinase pathwaysNCI-H460 lung cancer cellsFnIII-1cFirst Type III domainNon-small cell lung cancer cellsTRAIL-induced apoptosisΑvβ5 integrin receptorLung cancer resistanceCell lung cancer cellsHuman lung cancer cellsKinase pathwayCancer cell resistanceIntegrin activationCaspase-8Signaling pathwaysFibronectin matrixSensitive proteinsThe Fibronectin III‐1 Domain Activates a PI3‐Kinase/Akt Signaling Pathway Leading to αvβ5 Integrin Activation and TRAIL Resistance in Human Lung Cancer Cells
Cho C, McKeown‐Longo P. The Fibronectin III‐1 Domain Activates a PI3‐Kinase/Akt Signaling Pathway Leading to αvβ5 Integrin Activation and TRAIL Resistance in Human Lung Cancer Cells. The FASEB Journal 2016, 30: lb82-lb82. DOI: 10.1096/fasebj.30.1_supplement.lb82.Peer-Reviewed Original ResearchLung cancer cellsTRAIL resistanceNon-small cell lung cancerH460 lung cancer cellsCancer cellsCell lung cancerHuman lung cancer cellsLung cancer resistancePI3K/Akt pathwayTumor-stroma interfaceCancer cell resistanceAkt Signaling PathwayΑvβ5 integrin receptorLung cancerImmunohistochemical stainingTumor stromaFirst Type III domainFnIII-1cDrug resistanceBlood vesselsAkt pathwayCancer resistanceSignaling pathwaysFibronectin contributesSubsequent apoptosis
2015
Cryptic activity within the Type III1 domain of fibronectin regulates tissue inflammation and angiogenesis.
Cho C, Kelsh-Lasher R, Ambesi A, McKeown-Longo PJ. Cryptic activity within the Type III1 domain of fibronectin regulates tissue inflammation and angiogenesis. Current Topics In Peptide & Protein Research 2015, 16: 37-47. PMID: 27524870, PMCID: PMC4981920.Peer-Reviewed Original Research