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 differentiationMetastasis 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 DOI: 10.7554/elife.97279.3.Peer-Reviewed Original ResearchCancer cellsDickkopf-2Promoter region of Sox9Analysis 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 targets
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
2020
Calcium metabolism and breast cancer: Echoes of lactation?
Grinman D, Athonvarungkul D, Wysolmerski J, Jeong J. Calcium metabolism and breast cancer: Echoes of lactation? Current Opinion In Endocrine And Metabolic Research 2020, 15: 63-70. PMID: 33299957, PMCID: PMC7720883, DOI: 10.1016/j.coemr.2020.11.006.BooksBreast cancerSystemic calcium homeostasisBreast cancer cellsMaternal calciumMammary epithelial cellsCalcium metabolismBone metabolismSystemic metabolismIntracellular calciumMalignant behaviorCalcium homeostasisCalcium receptorCalcium secretionSeries of adaptationsUptake of calciumMammary glandEpithelial cellsCalcium transportCancer cellsCell proliferationExtracellular fluidCancerCalciumMetabolismLactation
2019
NHERF1 Is Required for Localization of PMCA2 and Suppression of Early Involution in the Female Lactating Mammary Gland
Jeong J, Kim W, Hens J, Dann P, Schedin P, Friedman PA, Wysolmerski JJ. NHERF1 Is Required for Localization of PMCA2 and Suppression of Early Involution in the Female Lactating Mammary Gland. Endocrinology 2019, 160: 1797-1810. PMID: 31087002, PMCID: PMC6619491, DOI: 10.1210/en.2019-00230.Peer-Reviewed Original ResearchConceptsPlasma membrane calcium ATPase 2Mammary epithelial cellsSpecialized plasma membrane domainsMammary epithelial cell deathLuminal epithelial cellsCell deathPremature mammary gland involutionBreast cancer cellsApical-basal polarityEpithelial cellsPlasma membrane domainsApical membraneSecretory luminal epithelial cellsExchanger regulatory factor 1Cell death pathwaysNHERF1 expressionMammary gland involutionCancer cellsRegulatory factor 1Sodium-hydrogen exchanger regulatory factor-1Lactating Mammary GlandNormal mammary epithelial cellsMembrane localizationEpithelial cell deathMembrane domains
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 knockdown
2017
The 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 in Breast Physiology and Cancer
Kim W, Wysolmerski JJ. Calcium-Sensing Receptor in Breast Physiology and Cancer. Frontiers In Physiology 2016, 7: 440. PMID: 27746743, PMCID: PMC5043011, DOI: 10.3389/fphys.2016.00440.BooksBreast cancer cellsPTHrP productionCancer cellsInhibits cell deathMammary epithelial cellsEpithelial cellsG-protein usageBreast cancer cell proliferationElevated extracellular calcium levelsOsteolytic bone metastasesNormal breast epithelial cellsNuclear pathwaysCalcium sensing receptorCalcium-sensing receptorBreast epithelial cellsBreast cancer progressionCancer cell proliferationExtracellular calcium levelsNormal breast cellsProtein secretionCell deathCancer progressionBone metastasesPTHrP secretionCellular proliferationCalcium-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
The 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 calcium
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 surfaceExpressionOverexpression
2009
The calcium-sensing receptor couples to Gαs and regulates PTHrP and ACTH secretion in pituitary cells
Mamillapalli R, Wysolmerski J. The calcium-sensing receptor couples to Gαs and regulates PTHrP and ACTH secretion in pituitary cells. Journal Of Endocrinology 2009, 204: 287-297. PMID: 20032198, PMCID: PMC3777408, DOI: 10.1677/joe-09-0183.Peer-Reviewed Original ResearchConceptsG protein-coupled receptorsACTH secretionCAMP productionProtein-coupled receptorsDifferent G proteinsCaR couplesAtT-20 cellsHormone secretionExtracellular calciumSystemic calcium homeostasisBiological functionsG proteinsBreast cancer cellsCell typesCalcium-sensing receptorCell growthReceptors coupleMalignant breast cellsCancer cellsKidney cellsBreast cellsCAR activationPituitary corticotrophsCalcium homeostasisAnterior pituitary
2008
Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells*
Mamillapalli R, VanHouten J, Zawalich W, Wysolmerski J. Switching of G-protein Usage by the Calcium-sensing Receptor Reverses Its Effect on Parathyroid Hormone-related Protein Secretion in Normal Versus Malignant Breast Cells*. Journal Of Biological Chemistry 2008, 283: 24435-24447. PMID: 18621740, PMCID: PMC2528989, DOI: 10.1074/jbc.m801738200.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBone NeoplasmsBreast NeoplasmsCell Line, TumorCyclic AMPCyclic AMP-Dependent Protein KinasesFemaleGTP-Binding Protein alpha SubunitsHumansHypercalcemiaLactationMammary Glands, AnimalMammary Neoplasms, AnimalMAP Kinase Signaling SystemMiceNeoplasm MetastasisNeoplasm ProteinsParathyroid Hormone-Related ProteinPregnancyReceptors, Calcium-SensingType C PhospholipasesConceptsG-protein usagePTHrP productionMammary epithelial cellsBreast cancer cellsBreast cellsMCF-7 cellsParathyroid hormone-related protein secretionParathyroid hormone-related proteinParathyroid hormone secretionCancer cellsMCF-7 human breast cancer cellsCalcium-sensing receptorHuman breast cancer cellsHormone-related proteinNormal mammary epithelial cellsRegulation of calciumMalignant breast cellsNormal breast cellsG protein-coupled receptorsG protein couplingBone metastasesPTHrP secretionHormone secretionBone metabolismBreast cancer
2002
Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*
Wysolmerski JJ, Dann PR, Zelazny E, Dunbar ME, Insogna KL, Guise TA, Perkins AS. Overexpression of Parathyroid Hormone‐Related Protein Causes Hypercalcemia but Not Bone Metastases in a Murine Model of Mammary Tumorigenesis*. Journal Of Bone And Mineral Research 2002, 17: 1164-1170. PMID: 12096830, DOI: 10.1359/jbmr.2002.17.7.1164.Peer-Reviewed Original ResearchConceptsBone metastasesBreast cancer cellsCancer cellsTransgenic miceTumor-bearing transgenic miceParathyroid hormone-related proteinPrimary breast cancerProduction of PTHrPHormone-related proteinWild-type littermatesEffects of PTHrPCause hypercalcemiaWild-type controlsVisceral metastasesSkeletal metastasesParathyroid hormoneBone resorptionArterial circulationBreast cancerDMBA treatmentMammary carcinogenImmunodeficient miceMammary tumorigenesisMurine modelHigh incidence