2023
HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway by regulating MSK1 and PPP2R2B
Malvi P, Chava S, Cai G, Hu K, Zhu L, Edwards Y, Green M, Gupta R, Wajapeyee N. HOXC6 drives a therapeutically targetable pancreatic cancer growth and metastasis pathway by regulating MSK1 and PPP2R2B. Cell Reports Medicine 2023, 4: 101285. PMID: 37951219, PMCID: PMC10694669, DOI: 10.1016/j.xcrm.2023.101285.Peer-Reviewed Original ResearchConceptsPancreatic ductal adenocarcinomaHomeobox C6PDAC growthInsulin-like growth factor 1 receptorGrowth factor 1 receptorKinase MSK1Factor 1 receptorTranscription factorsPancreatic cancer growthMSK1Tumor growthPDAC tumor growthMost pancreatic ductal adenocarcinomasMammalian targetIGF1R inhibitorsTherapeutic vulnerabilitiesRapamycin (mTOR) pathway activationMEK inhibitor trametinibMetastasis pathwaysPDAC mouse modelPDAC cellsMTOR inhibitionPharmacological inhibitionPathway activationInhibition blocks
2020
KLF7 promotes pancreatic cancer growth and metastasis by up-regulating ISG expression and maintaining Golgi complex integrity
Gupta R, Malvi P, Parajuli KR, Janostiak R, Bugide S, Cai G, Zhu LJ, Green MR, Wajapeyee N. KLF7 promotes pancreatic cancer growth and metastasis by up-regulating ISG expression and maintaining Golgi complex integrity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 12341-12351. PMID: 32430335, PMCID: PMC7275752, DOI: 10.1073/pnas.2005156117.Peer-Reviewed Original ResearchConceptsGolgi complex integrityGolgi complex fragmentationKrüppel-like factor 7Complex integrityPDAC growthMAP kinase pathwayTumor suppressor p53Protein glycosylationPancreatic ductal adenocarcinomaKinase pathwayPancreatic cancer growthSuppressor p53PDAC tumor growthTumor growthISG expressionProtein 3Factor 7Cancer growthKLF7 expressionComplex fragmentationKnockdownPharmacologic activationGrowth factorCell culturesExpression
2019
Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression
Malvi P, Janostiak R, Nagarajan A, Cai G, Wajapeyee N. Loss of thymidine kinase 1 inhibits lung cancer growth and metastatic attributes by reducing GDF15 expression. PLOS Genetics 2019, 15: e1008439. PMID: 31589613, PMCID: PMC6797230, DOI: 10.1371/journal.pgen.1008439.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinoma of LungAdultAgedAnimalsBiomarkers, TumorCell Line, TumorCell MovementCell ProliferationDatasets as TopicDNA-Binding ProteinsFemaleGene Expression Regulation, NeoplasticGene Knockdown TechniquesGrowth Differentiation Factor 15HumansLungLung NeoplasmsMaleMiceMiddle AgedNeoplasm Recurrence, LocalPrognosisSurvival AnalysisThymidine KinaseTranscription FactorsXenograft Model Antitumor AssaysConceptsShort hairpin RNALUAD cellsMetastatic attributesRho GTPase activityMAP kinase pathwayEctopic expressionGTPase activityTranscriptional overexpressionKinase pathwayKinase 1Cancer cell growthGenetic knockdownProfiling-based approachDifferentiation factor 15Hairpin RNALung adenocarcinoma patientsLung cancer growthCell growthLUAD therapyDownstream mediatorLUAD tumorsLUAD growthKey hallmarksReduced expressionDependent manner
2017
Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport
Nagarajan A, Dogra SK, Sun L, Gandotra N, Ho T, Cai G, Cline G, Kumar P, Cowles RA, Wajapeyee N. Paraoxonase 2 Facilitates Pancreatic Cancer Growth and Metastasis by Stimulating GLUT1-Mediated Glucose Transport. Molecular Cell 2017, 67: 685-701.e6. PMID: 28803777, PMCID: PMC5567863, DOI: 10.1016/j.molcel.2017.07.014.Peer-Reviewed Original ResearchMeSH KeywordsAMP-Activated Protein KinasesAnimalsAntineoplastic AgentsApoptosis Regulatory ProteinsAryldialkylphosphataseCarcinoma, Pancreatic DuctalCell Line, TumorCell MovementCell ProliferationEnergy MetabolismFemaleForkhead Box Protein O3Gene Expression Regulation, NeoplasticGlucoseGlucose Transporter Type 1HumansLiver NeoplasmsLung NeoplasmsMaleMice, NudeMutationPancreatic NeoplasmsProtein Kinase InhibitorsProto-Oncogene ProteinsProto-Oncogene Proteins p21(ras)RNA InterferenceSignal TransductionTime FactorsTranscription, GeneticTransfectionTumor BurdenTumor Suppressor Protein p53Xenograft Model Antitumor AssaysConceptsPDAC tumor growthGlucose transportCellular starvation responsesParaoxonase 2Glutamine metabolism pathwayNew metabolic regulatorPDAC tumor samplesShort hairpin RNATumor growthStarvation responseMetabolic genesTranscriptional targetsProtein kinaseTractable pathwayPancreatic cancer growthGenetic activationMetabolism pathwaysHairpin RNAMetabolic regulatorNew modulatorsHuman cancersPancreatic ductal adenocarcinomaMetabolic deregulationAMPKCancer growth
2014
Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1
Pirazzoli V, Nebhan C, Song X, Wurtz A, Walther Z, Cai G, Zhao Z, Jia P, de Stanchina E, Shapiro EM, Gale M, Yin R, Horn L, Carbone DP, Stephens PJ, Miller V, Gettinger S, Pao W, Politi K. Acquired Resistance of EGFR-Mutant Lung Adenocarcinomas to Afatinib plus Cetuximab Is Associated with Activation of mTORC1. Cell Reports 2014, 7: 999-1008. PMID: 24813888, PMCID: PMC4074596, DOI: 10.1016/j.celrep.2014.04.014.Peer-Reviewed Original ResearchMeSH KeywordsAdenocarcinomaAdenocarcinoma of LungAfatinibAnimalsAntibodies, Monoclonal, HumanizedAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorCetuximabDrug Resistance, NeoplasmErbB ReceptorsHumansLung NeoplasmsMechanistic Target of Rapamycin Complex 1MiceMice, NudeMice, TransgenicMultiprotein ComplexesMutationQuinazolinesRandom AllocationTOR Serine-Threonine KinasesXenograft Model Antitumor AssaysConceptsTyrosine kinase inhibitorsFirst-generation tyrosine kinase inhibitorEGFR-mutant lung adenocarcinomaLung adenocarcinomaMechanisms of resistanceEGFR antibody cetuximabPotential therapeutic strategyBiopsy specimensAntibody cetuximabDrug combinationsMouse modelTherapeutic strategiesAfatinibAddition of rapamycinCetuximabDual inhibitionAcquired ResistanceKinase inhibitorsGenomic alterationsAdenocarcinomaPatientsActivationGenomic mechanismsDrugsMTORC1 activation