2024
Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties.
Shin J, Park J, Lim J, Jeong J, Dinesh R, Maher S, Kim J, Park S, Hong J, Wysolmerski J, Choi J, Bothwell A. Metastasis of colon cancer requires Dickkopf-2 to generate cancer cells with Paneth cell properties. ELife 2024, 13 PMID: 39535280, PMCID: PMC11560131, DOI: 10.7554/elife.97279.Peer-Reviewed Original ResearchConceptsCancer cellsDickkopf-2Analysis of transcriptomeGeneration of cancer cellsPositive cancer cellsStem cell niche factorsColon cancer cellsPaneth cell differentiationHepatocyte nuclear factor 4 alphaLysozyme positive cellsChromatin accessibilityHNF4A proteinSingle-cell RNA sequencing analysisCell propertiesPaneth cell markersSequence analysisChromatin immunoprecipitationPromoter regionTranscription factorsTranscriptome analysisColon cancerColon cancer metastasisReduction of liver metastasisDownstream targetsCell differentiation
2022
Cancer-Associated Hypercalcemia. Reply.
Guise TA, Wysolmerski JJ. Cancer-Associated Hypercalcemia. Reply. New England Journal Of Medicine 2022, 386: 2540. PMID: 35767456, DOI: 10.1056/nejmc2206287.Peer-Reviewed Original ResearchPTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development
Grinman DY, Boras-Granic K, Takyar FM, Dann P, Hens JR, Marmol C, Lee J, Choi J, Chodosh LA, Sola MEG, Wysolmerski JJ. PTHrP induces STAT5 activation, secretory differentiation and accelerates mammary tumor development. Breast Cancer Research 2022, 24: 30. PMID: 35440032, PMCID: PMC9020078, DOI: 10.1186/s13058-022-01523-1.Peer-Reviewed Original ResearchConceptsOverexpression of PTHrPSecretory differentiationEpithelial cellsPTHrP overexpressionTumor latencyBreast cancerMammary epithelial cellsType 1 PTH/PTHrP receptorMMTV-PyMT breast cancer modelPTH/PTHrP receptorMMTV-PyMT miceMammary tumor developmentBreast cancer riskBreast cancer biologyExpression of PTHrPHormone-related proteinHuman breast cancerBreast cancer modelE74-like factor 5Normal mammary epithelial cellsBreast cancer progressionMouse mammary tumorsExpression of markersAlveolar epithelial cellsLuminal epithelial cellsCancer-Associated Hypercalcemia
Guise TA, Wysolmerski JJ. Cancer-Associated Hypercalcemia. New England Journal Of Medicine 2022, 386: 1443-1451. PMID: 35417639, DOI: 10.1056/nejmcp2113128.Peer-Reviewed Original Research
2021
MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells
Jeong J, Shin JH, Li W, Hong JY, Lim J, Hwang JY, Chung JJ, Yan Q, Liu Y, Choi J, Wysolmerski J. MAL2 mediates the formation of stable HER2 signaling complexes within lipid raft-rich membrane protrusions in breast cancer cells. Cell Reports 2021, 37: 110160. PMID: 34965434, PMCID: PMC8762588, DOI: 10.1016/j.celrep.2021.110160.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic Agents, ImmunologicalBreast NeoplasmsCell ProliferationCytoskeletal ProteinsDrug Resistance, NeoplasmEndocytosisFemaleHumansMembrane MicrodomainsMyelin and Lymphocyte-Associated Proteolipid ProteinsPhosphoproteinsPlasma Membrane Calcium-Transporting ATPasesReceptor, ErbB-2Sodium-Hydrogen ExchangersTrastuzumabTumor Cells, CulturedConceptsLipid raft formationBreast cancer cellsLipid raftsLipid raft resident proteinsCancer cellsRaft formationRaft-resident proteinsProximity ligation assayProtein complexesMembrane protrusionsProtein interactionsPlasma membraneLigation assayMAL2Membrane stabilityStructural organizationPotential therapeutic targetPhysical interactionMembrane retentionProteinRaftsTherapeutic targetCellsIntracellular calcium concentrationLow intracellular calcium concentration
2018
Inhibition of ezrin causes PKCα-mediated internalization of erbb2/HER2 tyrosine kinase in breast cancer cells
Jeong J, Choi J, Kim W, Dann P, Takyar F, Gefter JV, Friedman PA, Wysolmerski J. Inhibition of ezrin causes PKCα-mediated internalization of erbb2/HER2 tyrosine kinase in breast cancer cells. Journal Of Biological Chemistry 2018, 294: 887-901. PMID: 30463939, PMCID: PMC6341383, DOI: 10.1074/jbc.ra118.004143.Peer-Reviewed Original ResearchConceptsBreast cancer cellsBreast cancerCancer cellsHER2-positive breast cancer cell linesHER2-positive breast cancer cellsInvasive breast cancerDegradation of HER2Breast cancer cell linesHuman breast cancerNormal mammary epithelial cellsInhibition of EzrinHER2 tyrosine kinaseErbB family membersPMCA2 levelsCancer cell linesDuctal carcinomaHER2 expressionHER2 levelsMammary epithelial cellsHER2Human patientsPharmacologic inhibitionActive HER2Ezrin expressionGenetic knockdownAdipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation
Zwick RK, Rudolph MC, Shook BA, Holtrup B, Roth E, Lei V, Van Keymeulen A, Seewaldt V, Kwei S, Wysolmerski J, Rodeheffer MS, Horsley V. Adipocyte hypertrophy and lipid dynamics underlie mammary gland remodeling after lactation. Nature Communications 2018, 9: 3592. PMID: 30181538, PMCID: PMC6123393, DOI: 10.1038/s41467-018-05911-0.Peer-Reviewed Original ResearchConceptsMouse mammary glandMilk-producing epithelial cellsTissue-specific rolesMammary glandAdipose growthLipid dynamicsGenetic tracingPhysiological examplesFunctional implicationsCellular mechanismsAdipocyte hypertrophyMature adipocytesEssential roleVivo analysisTissue functionMammary epitheliumAdipocytesEpithelial cellsAdipocyte precursorsSubsequent involutionMilk lipidsPrimary mechanismMechanismLipidomicsMilk fat production
2017
HER2 signaling regulates HER2 localization and membrane retention
Jeong J, Kim W, Kim LK, VanHouten J, Wysolmerski JJ. HER2 signaling regulates HER2 localization and membrane retention. PLOS ONE 2017, 12: e0174849. PMID: 28369073, PMCID: PMC5378417, DOI: 10.1371/journal.pone.0174849.Peer-Reviewed Original ResearchMeSH KeywordsAntineoplastic AgentsApoptosisBreast NeoplasmsCalciumCell Line, TumorCell MembraneCell ProliferationErbB ReceptorsGene Knockdown TechniquesHumansIntracellular SpaceLapatinibPlasma Membrane Calcium-Transporting ATPasesQuinazolinesReceptor, ErbB-2Receptor, ErbB-3RNA, Small InterferingUbiquitinationConceptsMembrane protrusionsCell surfaceSpecific plasma membrane domainsPlasma membrane domainsReceptor tyrosine kinasesMembrane domainsErbB family membersErbB3/HER3Tyrosine kinaseGenetic knockdownHER2 ubiquitinationHER2/HER3PMCA2 expressionPharmacologic inhibitionUbiquitinationERBB2 geneHsp90HER2/EGFRCalcium pumpMembrane retentionInternalizationHuman breast cancerFamily membersHER3ExpressionThe scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2
Jeong J, VanHouten JN, Kim W, Dann P, Sullivan C, Choi J, Sneddon WB, Friedman PA, Wysolmerski JJ. The scaffolding protein NHERF1 regulates the stability and activity of the tyrosine kinase HER2. Journal Of Biological Chemistry 2017, 292: 6555-6568. PMID: 28235801, PMCID: PMC5399107, DOI: 10.1074/jbc.m116.770883.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid MotifsAnimalsApoptosisBreast NeoplasmsCalciumCell Line, TumorCell MembraneCell ProliferationFemaleGene Expression ProfilingGene Expression Regulation, NeoplasticGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansMiceMicroscopy, FluorescencePhosphoproteinsPlasma Membrane Calcium-Transporting ATPasesReceptor, ErbB-2RNA, MessengerSignal TransductionSodium-Hydrogen ExchangersConceptsBreast cancerHER2-positive breast cancerHER2-positive statusInvasive breast cancerHuman ductal carcinomaDegradation of HER2Normal mammary epithelial cellsMalignant breast cellsBreast cancer cellsErbB2/HER2Tyrosine kinase HER2Sodium-hydrogen exchanger regulatory factor-1Ductal carcinomaHER2 expressionExchanger regulatory factor 1Mammary epithelial cellsHER2Regulatory factor 1NHERF1 expressionBreast cellsEpithelial cellsCancerCancer cellsFactor 1PMCA2
2016
Calcium-Sensing Receptor Promotes Breast Cancer by Stimulating Intracrine Actions of Parathyroid Hormone–Related Protein
Kim W, Takyar FM, Swan K, Jeong J, VanHouten J, Sullivan C, Dann P, Yu H, Fiaschi-Taesch N, Chang W, Wysolmerski J. Calcium-Sensing Receptor Promotes Breast Cancer by Stimulating Intracrine Actions of Parathyroid Hormone–Related Protein. Cancer Research 2016, 76: 5348-5360. PMID: 27450451, PMCID: PMC5026591, DOI: 10.1158/0008-5472.can-15-2614.Peer-Reviewed Original ResearchConceptsMMTV-PyMT miceBreast cancer cellsCaSR activationBone metastasesBreast cancerInhibited tumor cell proliferationOsteolytic bone metastasesCancer cellsHuman breast cancer cell linesCalcium-sensing receptorHuman breast cancer cellsHormone-related proteinTransgenic mouse modelBreast cancer cell linesMMTV-PyMT transgenic mouse modelBreast cancer progressionTumor cell proliferationTumor cell growthCancer cell linesPTHrP levelsTissue-specific disruptionHigh extracellular concentrationsPTHrP productionCASR genePTHrP expressionPMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer
Jeong J, VanHouten JN, Dann P, Kim W, Sullivan C, Yu H, Liotta L, Espina V, Stern DF, Friedman PA, Wysolmerski JJ. PMCA2 regulates HER2 protein kinase localization and signaling and promotes HER2-mediated breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2016, 113: e282-e290. PMID: 26729871, PMCID: PMC4725473, DOI: 10.1073/pnas.1516138113.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBreast NeoplasmsCalciumCarcinogenesisCell Line, TumorCell MembraneCell ProliferationCell SurvivalEndocytosisFemaleFluorescent Antibody TechniqueForkhead Box Protein O1Forkhead Transcription FactorsGene Knockdown TechniquesHSP90 Heat-Shock ProteinsHumansImmunoblottingIntracellular SpaceMammary Neoplasms, AnimalMicePlasma Membrane Calcium-Transporting ATPasesProtein BindingProtein TransportReceptor, ErbB-2Signal TransductionSurvival AnalysisConceptsBreast cancerHigh tumor levelsDegradation of HER2Increases Intracellular CalciumMouse mammary tumor virusBreast cancer cellsMammary tumor virusPMCA2 levelsNeu miceTumor levelsFormation of tumorsHER2 levelsIntracellular calciumTherapeutic targetBreast tumorsHER2Milk calciumExpression correlatesCancerHSP 90Mammary glandCancer cellsTumor virusTumorsCalcium
2013
Parathyroid Hormone-Related Protein Specifies the Mammary Mesenchyme and Regulates Embryonic Mammary Development
Hiremath M, Wysolmerski J. Parathyroid Hormone-Related Protein Specifies the Mammary Mesenchyme and Regulates Embryonic Mammary Development. Journal Of Mammary Gland Biology And Neoplasia 2013, 18: 171-177. PMID: 23640717, PMCID: PMC3696739, DOI: 10.1007/s10911-013-9283-7.BooksConceptsParathyroid hormoneBreast cancerMammary rudimentsMammary budLoss of PTHrPOverexpression of PTHrPRole of PTHrPEffects of PTHrPNovel breast cancer susceptibility lociEpithelial-stromal crosstalkEmbryonic mammary budBreast cancer susceptibility lociEmbryonic mammary developmentMammary gland morphogenesisNipple skinDay 15PTHrP’s rolePTHrPMammary developmentMammary epithelial identityMammary mesenchymeCancer susceptibility lociCancerCritical regulatorHormoneThe calcium-sensing receptor in the breast
VanHouten JN, Wysolmerski JJ. The calcium-sensing receptor in the breast. Best Practice & Research Clinical Endocrinology & Metabolism 2013, 27: 403-414. PMID: 23856268, PMCID: PMC3713417, DOI: 10.1016/j.beem.2013.02.011.BooksConceptsG-protein usageBreast cancer cellsCalcium-sensing receptorCalcium metabolismCancer cellsParathyroid hormone-related protein levelsBreast cellsMaternal calcium metabolismOsteolytic skeletal metastasesSystemic calcium metabolismEpithelial cellsNormal breast epithelial cellsFeed-forward cycleMalignant breast cellsNormal breast cellsBreast epithelial cellsSkeletal metastasesPTHrP productionPTHrP expressionMammary epithelial cellsCaSRCalcium transportProtein levelsTransport of calciumSupply of calciumAttacking Breast Cancer at the Preinvasion Stage by Targeting Autophagy
Espina V, Wysolmerski J, Edmiston K, Liotta LA. Attacking Breast Cancer at the Preinvasion Stage by Targeting Autophagy. Women's Health 2013, 9: 157-170. PMID: 23477322, PMCID: PMC3779365, DOI: 10.2217/whe.13.5.BooksConceptsBreast cancerBreast cancer stem-like cellsCancer stem-like cellsBreast carcinoma cellsStem-like cellsDuctal carcinomaPreinvasive carcinomaPreinvasive neoplasmsClinical trialsIntracellular calciumSevere hypoxicTherapeutic strategiesNeoplastic cellsCarcinoma cellsMetabolic stressCarcinomaTherapyCancerCellsSurvival mechanismAutophagyNeoplasmsTrialsHypoxicOsteocytes remove and replace perilacunar mineral during reproductive cycles
Wysolmerski JJ. Osteocytes remove and replace perilacunar mineral during reproductive cycles. Bone 2013, 54: 230-236. PMID: 23352996, PMCID: PMC3624069, DOI: 10.1016/j.bone.2013.01.025.BooksConceptsBone lossLevels of PTHrPNegative calcium balanceLevels of estrogenPrincipal bone-resorbing cellsSkeletal calcium storesBone-resorbing cellsPTHrP levelsBone turnoverBone resorptionBone massMineral metabolismCalcium balanceRole of osteocytesCalcium storesMineral homeostasisOsteocytic osteolysisReproductive cycleOsteocytesSystemic demandsPericanalicular matrixCalciumLactationBone
2012
Parathyroid Hormone-Related Protein: An Update
Wysolmerski JJ. Parathyroid Hormone-Related Protein: An Update. The Journal Of Clinical Endocrinology & Metabolism 2012, 97: 2947-2956. PMID: 22745236, PMCID: PMC3431578, DOI: 10.1210/jc.2012-2142.BooksConceptsType 1 PTH/PTHrP receptorPTH/PTHrP receptorCauses of hypercalcemiaCommon paraneoplastic syndromeParaneoplastic syndromeHumoral hypercalcemiaParathyroid hormonePTHrP receptorBreast cancerNormal physiological functionPTHrPDisease statesTranslational researchHypercalcemiaOsteoporosisBedsidePhysiological functionsRelated genesHyperparathyroidismBasic biologyDiabetesMalignancyOsteoarthritisSyndromePTHPTHrP and breast cancer: more than hypercalcemia and bone metastases
Boras-Granic K, Wysolmerski JJ. PTHrP and breast cancer: more than hypercalcemia and bone metastases. Breast Cancer Research 2012, 14: 307. PMID: 22546075, PMCID: PMC3446368, DOI: 10.1186/bcr3129.BooksConceptsBone metastasesBreast cancerMMTV-PyMT miceNormal breast developmentPrimary breast tumorsHormone-related proteinBreast cancer susceptibility genesNew breast cancer susceptibility genesCancer patientsPrimary tumorCancer susceptibility genesClinical investigationBreast developmentBreast tumorsTumor growthPTHrPMetastasisHypercalcemiaTumorsCancerSusceptibility genesFurther researchPatientsMice
2010
PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer
VanHouten J, Sullivan C, Bazinet C, Ryoo T, Camp R, Rimm DL, Chung G, Wysolmerski J. PMCA2 regulates apoptosis during mammary gland involution and predicts outcome in breast cancer. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 11405-11410. PMID: 20534448, PMCID: PMC2895115, DOI: 10.1073/pnas.0911186107.Peer-Reviewed Original ResearchConceptsPMCA2 expressionBreast cancerT47D breast cancer cellsIntracellular calcium levelsBreast cancer progressionBreast cancer cellsEpithelial cell apoptosisPoor outcomeIntracellular calciumCalcium levelsMammary gland involutionCancer progressionCell apoptosisCancer cellsMammary involutionApoptosisGland involutionCancerMammary epithelial cell apoptosisOutcomesPMCA2Triggers apoptosisApical surfaceExpressionOverexpressionInteractions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation
Wysolmerski JJ. Interactions between breast, bone, and brain regulate mineral and skeletal metabolism during lactation. Annals Of The New York Academy Of Sciences 2010, 1192: 161-169. PMID: 20392232, PMCID: PMC3777748, DOI: 10.1111/j.1749-6632.2009.05249.x.BooksCharacterization of the Six1 homeobox gene in normal mammary gland morphogenesis
Coletta RD, McCoy EL, Burns V, Kawakami K, McManaman JL, Wysolmerski JJ, Ford HL. Characterization of the Six1 homeobox gene in normal mammary gland morphogenesis. BMC Developmental Biology 2010, 10: 4. PMID: 20074369, PMCID: PMC2823684, DOI: 10.1186/1471-213x-10-4.Peer-Reviewed Original ResearchConceptsNormal mammary gland developmentAdult mammary glandMammary gland developmentMammary glandMammary developmentBreast cancerMouse modelBreast tumorigenesisEmbryonic mammary glandPostnatal mammary developmentRag1-/- miceNormal mammary gland morphogenesisGland developmentTransgenic mouse modelBreast cancer initiationViable therapeutic targetIndependent mouse modelsAdult mouse mammary glandAnti-cancer therapyMammary stem cellsFamily membersMouse mammary glandUnwanted side effectsRole of Six1Invasive carcinoma