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 targetsCancer-associated hypercalcemia signals through the hindbrain to cause anorexia
Grinman D, Dann P, Shanabrough M, Horvath T, Wysolmerski J. Cancer-associated hypercalcemia signals through the hindbrain to cause anorexia. Journal Of Bone Oncology 2024, 45: 100535. DOI: 10.1016/j.jbo.2024.100535.Peer-Reviewed Original ResearchIntracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution
Jeong J, Lee J, Talaia G, Kim W, Song J, Hong J, Yoo K, Gonzalez D, Athonvarangkul D, Shin J, Dann P, Haberman A, Kim L, Ferguson S, Choi J, Wysolmerski J. Intracellular calcium links milk stasis to lysosome-dependent cell death during early mammary gland involution. Cellular And Molecular Life Sciences 2024, 81: 29. PMID: 38212474, PMCID: PMC10784359, DOI: 10.1007/s00018-023-05044-8.Peer-Reviewed Original Research
2023
Crosstalk within a brain-breast-bone axis regulates mineral and skeletal metabolism during lactation
Athonvarangkul D, Wysolmerski J. Crosstalk within a brain-breast-bone axis regulates mineral and skeletal metabolism during lactation. Frontiers In Physiology 2023, 14: 1121579. PMID: 36875035, PMCID: PMC9979219, DOI: 10.3389/fphys.2023.1121579.Peer-Reviewed Original ResearchBone lossExcess bone lossExcessive bone lossPostmenopausal osteoporosisBone turnoverRare entityMineral metabolismSkeletal metabolismNew therapiesBone qualityCalcium demandOsteoporosisMammary glandCalcium deliveryBone axisReversible physiological responseLactationHormonal signalsCurrent knowledgeMetabolismPhysiological responsesPregnancyHypothalamusPathophysiologyTherapy
2022
PSAT208 A Case of Hypercalcemia From PTHrP-Producing Fibromyxoid Sarcoma Responsive to Glucocorticoid Therapy
Niu I, Hsiao E, Wustrack R, Wysolmerski J, Dann P, Masharani U. PSAT208 A Case of Hypercalcemia From PTHrP-Producing Fibromyxoid Sarcoma Responsive to Glucocorticoid Therapy. Journal Of The Endocrine Society 2022, 6: a212-a213. PMCID: PMC9624585, DOI: 10.1210/jendso/bvac150.436.Peer-Reviewed Original ResearchLow-grade fibromyxoid sarcomaPmol/L.Myositis ossificansZoledronic acidFibromyxoid sarcomaFDG PET/CT scansPET/CT scansParathyroid hormone-related proteinHigh-dose steroidsLarge heterogenous massLeft thigh massCase of hypercalcemiaMechanism of glucocorticoidHormone-related proteinPmol/LGiant cell reactionLeft adductor musclePTHrP gene expressionLong-term managementTumor-vessel interactionsGlucocorticoid therapyMethylprednisolone doseFDG avidityPTHrP levelsSerum light chainsCancer-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 concentrationThe butyrophilin 1a1 knockout mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation
Jeong J, Kadegowda AKG, Meyer TJ, Jenkins LM, Dinan JC, Wysolmerski JJ, Weigert R, Mather IH. The butyrophilin 1a1 knockout mouse revisited: Ablation of Btn1a1 leads to concurrent cell death and renewal in the mammary epithelium during lactation. FASEB BioAdvances 2021, 3: 971-997. PMID: 34938960, PMCID: PMC8664049, DOI: 10.1096/fba.2021-00059.Peer-Reviewed Original ResearchWild-type cellsAcute phase response genesCell death pathwaysMouse linesFos/JunMutant mouse linesMammary epitheliumMammary epithelial cellsButyrophilin 1A1Secretion complexDeath routeProteomic analysisNuclear DNADeath pathwaysResponse genesOptimal milk productionExpression of cyclinsCaspase-8Upregulation of Ki67Cell deathMembrane receptorsType cellsLipid dropletsRedox enzymesLysosomal lysis
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 fluidCancerCalciumMetabolismLactationChapter 14 The Onset and Maintenance of Human Lactation and its Endocrine Regulation
Sadovnikova A, Wysolmerski J, Hovey R. Chapter 14 The Onset and Maintenance of Human Lactation and its Endocrine Regulation. 2020, 189-205. DOI: 10.1016/b978-0-12-814823-5.00014-3.Peer-Reviewed Original ResearchEndocrine regulationCopious milk secretionMobilization of fatEpithelial tissuesBone storesMaternal adaptationProgesterone levelsEndocrine changesFood intakeBreast growthBreast epitheliumFetal developmentGlucose productionHuman lactationMilk secretionMammalian reproductionBreastPhysiological changesMother's bodyLactationOnsetTissueKey eventsMilk productionPregnancy
2019
Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression
Lotinun S, Ishihara Y, Nagano K, Kiviranta R, Carpentier VT, Neff L, Parkman V, Ide N, Hu D, Dann P, Brooks D, Bouxsein ML, Wysolmerski J, Gori F, Baron R. Cathepsin K-deficient osteocytes prevent lactation-induced bone loss and parathyroid hormone suppression. Journal Of Clinical Investigation 2019, 129: 3058-3071. PMID: 31112135, PMCID: PMC6668688, DOI: 10.1172/jci122936.Peer-Reviewed Original ResearchConceptsLactation-induced bone lossParathyroid hormoneBone lossBone resorptionCathepsin KMilk calcium levelsParathyroid hormone suppressionSerum parathyroid hormoneRegulation of PTHOsteoclastic bone resorptionTrabecular bone volumeOsteocyte lacunar areaHormone suppressionHigh calcium demandOsteoclast numberCortical thicknessEffect of lactationCalcium levelsNormal rangeBone volumeCalcium demandExact mechanismLacunar areaResorptionSufficient calciumNHERF1 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 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 productionChapter 46 Parathyroid Hormone, Parathyroid Hormone–Related Protein, and Calcitonin
Wysolmerski J. Chapter 46 Parathyroid Hormone, Parathyroid Hormone–Related Protein, and Calcitonin. 2018, 849-870. DOI: 10.1016/b978-0-12-809965-0.00046-x.Peer-Reviewed Original Research
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