2016
Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling
Pawar A, Meier JA, Dasgupta A, Diwanji N, Deshpande N, Saxena K, Buwa N, Inchanalkar S, Schwartz MA, Balasubramanian N. Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling. Cellular Signalling 2016, 28: 1225-1236. PMID: 27269287, PMCID: PMC4973806, DOI: 10.1016/j.cellsig.2016.05.023.Peer-Reviewed Original ResearchMeSH KeywordsADP-Ribosylation Factor 6ADP-Ribosylation FactorsAnimalsCell AdhesionCell Line, TumorCell ProliferationCell Transformation, NeoplasticEmbryo, MammalianExocytosisExtracellular Signal-Regulated MAP KinasesFibroblastsHumansMembrane MicrodomainsMiceProtein TransportRal GTP-Binding ProteinsSignal TransductionConceptsARF6 activationRegulatory crosstalkActive RalIntegrin-dependent regulationOncogenic H-RasIndependent growthIntegrin-dependent activationAdhesion-dependent pathwayKey downstream mediatorSmall GTPase RalActive RalABladder cancer T24 cellsDependent traffickingRal functionIsoforms functionRaft microdomainsOncogenic RasPlasma membraneDependent regulationH-RasArf6Dependent activationDependent pathwayDownstream mediatorVital mediators
2014
Integrin adjunct therapy for melanoma
Andarawewa KL, Moissoglu K, Lee C, Ando Y, Yu M, Debnath P, Shannon JD, Sirinivasan S, Conaway MR, Weber MJ, Schwartz MA. Integrin adjunct therapy for melanoma. Pigment Cell & Melanoma Research 2014, 28: 114-116. PMID: 25264294, PMCID: PMC6542633, DOI: 10.1111/pcmr.12320.Peer-Reviewed Original ResearchDiscovery and characterization of small molecules that target the GTPase Ral
Yan C, Liu D, Li L, Wempe MF, Guin S, Khanna M, Meier J, Hoffman B, Owens C, Wysoczynski CL, Nitz MD, Knabe WE, Ahmed M, Brautigan DL, Paschal BM, Schwartz MA, Jones DN, Ross D, Meroueh SO, Theodorescu D. Discovery and characterization of small molecules that target the GTPase Ral. Nature 2014, 515: 443-447. PMID: 25219851, PMCID: PMC4351747, DOI: 10.1038/nature13713.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsATP-Binding Cassette TransportersCell Line, TumorCell ProliferationComputer SimulationDrug Screening Assays, AntitumorFemaleGTPase-Activating ProteinsHumansMiceModels, MolecularMolecular Targeted TherapyNeoplasmsProtein BindingRal GTP-Binding ProteinsRas ProteinsSignal TransductionSmall Molecule LibrariesSubstrate SpecificityXenograft Model Antitumor AssaysTension-Sensitive Actin Assembly Supports Contractility at the Epithelial Zonula Adherens
Leerberg JM, Gomez GA, Verma S, Moussa EJ, Wu SK, Priya R, Hoffman BD, Grashoff C, Schwartz MA, Yap AS. Tension-Sensitive Actin Assembly Supports Contractility at the Epithelial Zonula Adherens. Current Biology 2014, 24: 1689-1699. PMID: 25065757, PMCID: PMC5103636, DOI: 10.1016/j.cub.2014.06.028.Peer-Reviewed Original ResearchConceptsMena/VASPActin assemblyEpithelial zonula adherensZonula adherensMyosin II activationActin filament turnoverCadherin junctionsActomyosin apparatusVASP proteinsActin scaffoldFilament turnoverActin filamentsJunctional integrityVinculinPhysical interactionTissue integrityActomyosin systemEpithelial cellsAdherensAssemblyContractile apparatusRegulationVASPEffective contractilityUnderlying mechanism
2012
Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment
Yaqoob U, Cao S, Shergill U, Jagavelu K, Geng Z, Yin M, de Assuncao TM, Cao Y, Szabolcs A, Thorgeirsson S, Schwartz M, Yang JD, Ehman R, Roberts L, Mukhopadhyay D, Shah VH. Neuropilin-1 Stimulates Tumor Growth by Increasing Fibronectin Fibril Assembly in the Tumor Microenvironment. Cancer Research 2012, 72: 4047-4059. PMID: 22738912, PMCID: PMC3421041, DOI: 10.1158/0008-5472.can-11-3907.Peer-Reviewed Original ResearchConceptsFibronectin fibril assemblyTumor growthTumor microenvironmentNeuropilin-1Fibril assemblyStromal myofibroblastsNonreceptor tyrosine kinase c-AblTyrosine kinase c-AblHuman cancer specimensNew molecular mechanismCancer cell invasionNRP-1 levelsSerine 612Intracellular associationExtracellular domainMatrix stiffnessMolecular mechanismsC-AblGenetic depletionMatrix proteinsCell invasionClinical outcomesCancer specimensTherapeutic targetingAntibody neutralizationp21-Activated kinase 4 promotes prostate cancer progression through CREB
Park M, Lee H, Lee C, You S, Kim D, Park B, Kang M, Heo W, Shin E, Schwartz M, Kim E. p21-Activated kinase 4 promotes prostate cancer progression through CREB. Oncogene 2012, 32: 2475-2482. PMID: 22710715, DOI: 10.1038/onc.2012.255.Peer-Reviewed Original ResearchConceptsP21-activated kinase 4Prostate cancer progressionProstate cancerCancer progressionLNCaP-FGC cellsPromising therapeutic targetKinase 4Prostate cancer cellsDU145 prostate cancer cellsSpecific protein kinase A (PKA) inhibitorProtein kinase A (PKA) inhibitorElevation of cAMPNeuroendocrine differentiationNude miceTherapeutic targetActive PAK4Downstream effector pathwaysTumor progressionDecreased expressionTumor formationCancerCancer cellsPC-3ProgressionEffector pathways
2011
Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer
Thomas S, Overdevest JB, Nitz MD, Williams PD, Owens CR, Sanchez-Carbayo M, Frierson HF, Schwartz MA, Theodorescu D. Src and Caveolin-1 Reciprocally Regulate Metastasis via a Common Downstream Signaling Pathway in Bladder Cancer. Cancer Research 2011, 71: 832-841. PMID: 21148751, PMCID: PMC4306590, DOI: 10.1158/0008-5472.can-10-0730.Peer-Reviewed Original ResearchConceptsActin stress fibersCav-1Active SrcStress fibersPhosphorylation of p190RhoGAPSrc protein levelsDownstream Signaling PathwaysCaveolin-1 expressionActivity of RhoACav-1 overexpressionTail vein inoculationRegulates MetastasisBladder cancerCommon downstreamHuman bladder cancer cellsPhosphorylated formSignaling pathwaysSrc levelsCell migrationBiochemical studiesLung metastasesMetastasis developmentSrc expressionBladder cancer cellsSrc
2009
Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function
Wu Y, Moissoglu K, Wang H, Wang X, Frierson HF, Schwartz MA, Theodorescu D. Src phosphorylation of RhoGDI2 regulates its metastasis suppressor function. Proceedings Of The National Academy Of Sciences Of The United States Of America 2009, 106: 5807-5812. PMID: 19321744, PMCID: PMC2667073, DOI: 10.1073/pnas.0810094106.Peer-Reviewed Original ResearchMeSH KeywordsCell Line, TumorDisease ProgressionGene Expression ProfilingGuanine Nucleotide Dissociation InhibitorsHumansImmunohistochemistryNeoplasm MetastasisPhosphorylationProtein BindingRho Guanine Nucleotide Dissociation Inhibitor betaRho-Specific Guanine Nucleotide Dissociation InhibitorsSrc-Family KinasesTumor Suppressor ProteinsUrinary Bladder NeoplasmsConceptsMetastasis suppressionSrc levelsSrc phosphorylation siteProtein interaction analysisMetastasis suppressor functionRhoGDI2 expressionSuppressor of metastasisGene expression profilingRhoGDI2 functionTyr-153Kinase bindsPhosphorylation sitesAmount of Rac1Expression profilingInteraction partnersSrc phosphorylationSrc inhibitorStable expressionBladder cancerSuppressor functionRhoGDI2Cancer cell linesCell membraneSrcPhosphorylation
2008
Integrin Agonists as Adjuvants in Chemotherapy for Melanoma
Schwartz MA, McRoberts K, Coyner M, Andarawewa KL, Frierson HF, Sanders JM, Swenson S, Markland F, Conaway MR, Theodorescu D. Integrin Agonists as Adjuvants in Chemotherapy for Melanoma. Clinical Cancer Research 2008, 14: 6193-6197. PMID: 18829498, DOI: 10.1158/1078-0432.ccr-08-1285.Peer-Reviewed Original ResearchConceptsMelanoma linesExtracellular matrixMetastatic melanomaM21 tumorsTherapeutic responseImmunodeficient miceTumor volumeChemotherapyClonal growth assaysTherapy resistanceTumor growthHuman melanomaChemotherapeutic efficacyMelanomaTumor cellsDrug 1Survival assaysM21 cellsM21 melanomaSmall nestsIntegrin agonistsIntegrin-dependent adhesionTumorsMiceSnake venom