https://m2.mtmt.hu/ hun 2026-05-31 15:43 JournalArticle 32165251 VALIDATED true Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States Department of Medicine, University of Maryland, Baltimore, MD, United States Department of Dermatology, Emory School of Medicine, Atlanta Veterans Administration Medical Center, Atlanta, GA, United States MTA TTK Momentum Cancer Biomarker Research Group, Budapest, Hungary Semmelweis University, Department of Bioinformatics and 2nd Department of Pediatrics, Budapest, Hungary Division of Endocrinology, Department of Medicine, Lenox Hill Hospital, New York, NY, United States Export Date: 8 November 2021 Correspondence Address: Sharma, D.; Department of Oncology, United States; email: dsharma7@jhmi.edu Chemicals/CAS: adiponectin, 283182-39-8; afimoxifene, 65213-48-1, 68392-35-8; cathepsin D, 9025-26-7; epidermal growth factor receptor, 79079-06-4; epidermal growth factor receptor 2, 137632-09-8; estradiol, 50-28-2; honokiol, 35354-74-6; tamoxifen, 10540-29-1; tamoxifen citrate, 54965-24-1 Funding details: National Cancer Institute, NCI, R01CA204555 Funding details: Avon Foundation for Women, AFW Funding details: Breast Cancer Research Foundation, BCRF, 90047965 Funding text 1: This work was supported by NCI NIH R01CA204555, Avon Foundation, Breast Cancer Research Foundation (BCRF) 90047965 (to DS). 0 false 2026-05-21T02:30:09.290+0000 2023-10-18T06:43:16.129+0000 2021-08-30T13:59:27.500+0000 true 10000109 Győrffy Balázs /api/author/10000109 Author Győrffy Balázs (Onkológia) true 10000109 2023-10-30T03:22:03.047+0000 2023-10-30T03:22:03.047+0000 2023-10-18T06:43:16.307+0000 true 10080205 Szalóky-Siki Ágnes /api/admin/10080205 Admin Szalóky-Siki Ágnes (SE_KK_Admin5_SZSA, admin) true true false true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle true 10000059 Article true 24 24 /api/publicationtype/24 PublicationType Folyóiratcikk 1 true 24 JournalArticle /api/subtype/10000059 Szakcikk SubType Szakcikk (Folyóiratcikk) 101 true 10000059 true 1 /api/category/1 Category Tudományos true 1 Nagalingam, A. true true /api/journal/10082192 REVIEWED NPJ BREAST CANCER 2374-4677 true false 10082192 false 10082192 true 2374-4677 Journal FOREIGN 7 1 105 105 13 2021 Obese women with hormone receptor-positive breast cancer exhibit poor response to therapy and inferior outcomes. However, the underlying molecular mechanisms by which obesity/hyperleptinemia may reduce the efficacy of hormonal therapy remain elusive. Obese mice with hyperleptinemia exhibit increased tumor progression and respond poorly to tamoxifen compared to non-obese mice. Exogenous leptin abrogates tamoxifen-mediated growth inhibition and potentiates breast tumor growth even in the presence of tamoxifen. Mechanistically, leptin induces nuclear translocation of phosphorylated-ER and increases the expression of ER-responsive genes, while reducing tamoxifen-mediated gene repression by abrogating tamoxifen-induced recruitment of corepressors NCoR, SMRT, and Mi2 and potentiating coactivator binding. Furthermore, in silico analysis revealed that coactivator Med1 potentially associates with 48 (out of 74) obesity-signature genes. Interestingly, leptin upregulates Med1 expression by decreasing miR-205, and increases its functional activation via phosphorylation, which is mediated by activation of Her2 and EGFR. It is important to note that Med1 silencing abrogates the negative effects of leptin on tamoxifen efficacy. In addition, honokiol or adiponectin treatment effectively inhibits leptin-induced Med1 expression and improves tamoxifen efficacy in hyperleptinemic state. These studies uncover the mechanistic insights how obese/hyperleptinemic state may contribute to poor response to tamoxifen implicating leptin-miR205-Med1 and leptin-Her2-EGFR-Med1 axes, and present bioactive compound honokiol and adipocytokine adiponectin as agents that can block leptin’s negative effect on tamoxifen. © 2021, The Author(s). true true 2021 true true true false true false GOLD 2026-05-21 true https://doi.org/10.1038/s41523-021-00314-9 18 0 18 16 0 17 18 15 16 18 18 16 16 16 2 0 18 16 18 16 0 2 2 Folyóiratcikk Journal Article 24 17 Könyvrészlet Chapter in Book 25 1 Könyv Book 23 0 Egyéb konferenciaközlemény Conference paper 31 0 Egyéb konferenciakötet Conference proceedings 32 0 Oltalmi formák Protection forms 26 0 Disszertáció Thesis 28 0 Egyéb Miscellaneous 29 0 Alkotás Achievement 22 0 Kutatási adat Research data 33 0 Folyóiratcikk Journal Article 24 0 0 0 Könyvrészlet Chapter in Book 25 0 0 0 Könyv Book 23 0 0 0 Egyéb konferenciaközlemény Conference paper 31 0 0 0 Egyéb konferenciakötet Conference proceedings 32 0 0 0 Oltalmi formák Protection forms 26 0 0 0 Disszertáció Thesis 28 0 0 0 Egyéb Miscellaneous 29 0 0 0 Alkotás Achievement 22 0 0 0 Kutatási adat Research data 33 0 0 0 2022 0 4 4 4 4 2023 0 7 7 7 7 2024 0 6 4 6 4 2025 0 1 1 1 1 D1 false false false false 2021-09-05T08:43:07.148+0000 Bioinformatika Tanszék (SE / AOK / I); II. Sz. Gyermekgyógyászati Klinika (SE / AOK / K); Onkológiai Biomarker Kutatócsoport (Lendület) (HRN TTK / MÉI) 1 26 3 10 0 true Language 10002 /api/language/10002 Angol Angol English true 2 true PersonAuthorship 97235374 /api/authorship/97235374 Nagalingam, A. 1 0.1 true false false Nagalingam A. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235375 /api/authorship/97235375 Siddharth, S. 2 0.1 false false false Siddharth S. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235376 /api/authorship/97235376 Parida, S. 3 0.1 false false false Parida S. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235377 /api/authorship/97235377 Muniraj, N. 4 0.1 false false false Muniraj N. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235378 /api/authorship/97235378 Avtanski, D. 5 0.1 false false false Avtanski D. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235379 /api/authorship/97235379 Kuppusamy, P. 6 0.1 false false false Kuppusamy P. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235380 /api/authorship/97235380 Elsey, J. 7 0.1 false false false Elsey J. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235381 /api/authorship/97235381 Arbiser, J.L. 8 0.1 false false false Arbiser J.L. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235382 /api/authorship/97235382 Győrffy, B. [Győrffy, Balázs (Onkológia), szerző] II. Sz. Gyermekgyógyászati Klinika (SE / AOK / K); Onkológiai Biomarker Kutatócsoport (Lendület) (HRN TTK / MÉI); Bioinformatika Tanszék (SE / AOK / I) 9 0.1 false false false Author 10000109 /api/author/10000109 Győrffy Balázs (Onkológia) Győrffy Balázs true 10000109 true Győrffy B. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PersonAuthorship 97235383 /api/authorship/97235383 Sharma, D. ✉ 10 0.1 false true true Sharma D. true false false AuthorshipType 1 /api/authorshiptype/1 Szerző 0 true 0 true false true PublicationIdentifier 19183595 /api/publicationidentifier/19183595 DOI: 10.1038/s41523-021-00314-9 PlainSource 6 /api/publicationsource/6 DOI PublicationSourceType 10001 /api/publicationsourcetype/10001 DOI true true true DOI DOI https://doi.org/@@@ true true 6 true GOLD true IDENTICAL 10.1038/s41523-021-00314-9 https://doi.org/10.1038/s41523-021-00314-9 false true PublicationIdentifier 19183596 /api/publicationidentifier/19183596 WoS: 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true Keyword 1500139 /api/keyword/1500139 microRNA 205 true true Keyword 1506663 /api/keyword/1506663 Mediator complex true true Keyword 1522846 /api/keyword/1522846 recombinant leptin true true Keyword 1533956 /api/keyword/1533956 receptor tyrosine kinase like orphan receptor true true Keyword 1564929 /api/keyword/1564929 honokiol true true Keyword 1746999 /api/keyword/1746999 afimoxifene true true Keyword 1877554 /api/keyword/1877554 tamoxifen citrate true true Keyword 2277709 /api/keyword/2277709 trefoil factor 1 true true Keyword 2340513 /api/keyword/2340513 MCF7/LCC1 cell line true true SjrRating 11231588 /api/sjrrating/11231588 sjr:D1 (2021) Scopus - Oncology NPJ BREAST CANCER 2374-4677 1880-4233 27 0.1 journal RatingType 10002 /api/ratingtype/10002 sjr sjr true true ClassificationExternal 2730 /api/classificationexternal/2730 Scopus - Oncology true 2730 true D1 DIRECT true true Reference 22574096 /api/reference/22574096 1. 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(2021) NPJ BREAST CANCER 2374-4677 7 1<div class="JournalArticle Publication long-list"> <div class="authors"> <img title="Forrásközlemény" style="float: left" src="/frontend/resources/grid/publication-core-icon.png"> <img title="Idézőközlemény" style="float: left" src="/frontend/resources/grid/publication-citation-icon.png"> <div class="autype autype0"> <span class="author-name" >Nagalingam A. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Siddharth S. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Parida S. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Muniraj N. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Avtanski D. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Kuppusamy P. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Elsey J. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Arbiser J.L. </span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" mtid="10000109"><a href="/gui2/?type=authors&mode=browse&sel=10000109" target="_blank">Győrffy B. (<span class="authorship-author-name">Győrffy Balázs</span> <span class="authorAux-mtmt"> Onkológia</span>) </a> </span> <span class="author-affil"><span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Klinikum">K</span>/II. Sz. Gyermekgyógyászati Klinika; <span title="Természettudományi Kutatóközpont">TTK</span>/<span title="Enzimológiai Intézet">EI</span>/Onkológiai Biomarker Kutatócsoport (Lendület); <span title="Semmelweis Egyetem">SE</span>/<span title="Általános Orvostudományi Kar">AOK</span>/<span title="Intézet">I</span>/Bioinformatika Tanszék</span> ;&nbsp;&nbsp;&nbsp; <span class="author-name" >Sharma D. ✉ </span> </div> </div> <div class="title"><a href="/gui2/?mode=browse&params=publication;32165251" target="_blank">Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB</a></div> <div> <span class="journal-title">NPJ BREAST CANCER</span> <span class="journal-issn">( <a target="_blank" href="https://portal.issn.org/resource/ISSN/2374-4677">2374-4677</a>)</span>: <span class="journal-volume">7</span> <span class="journal-issue">1</span> <span class="page"> Paper 105. 13 p. </span> <span class="year">(2021)</span> </div> <div class="pub-footer"> <span class="language" xmlns="http://www.w3.org/1999/html">Nyelv: Angol | </span> <span class="identifiers"> <span class="id identifier oa_GOLD" title=" Gold "> <a style="color:blue" title="10.1038/s41523-021-00314-9" target="_blank" href="https://doi.org/10.1038/s41523-021-00314-9"> DOI </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="000686654000001" target="_blank" href="https://www.webofscience.com/wos/woscc/full-record/000686654000001"> WoS </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="85112689423" target="_blank" href="http://www.scopus.com/record/display.url?origin=inward&eid=2-s2.0-85112689423"> Scopus </a> </span> <span class="id identifier oa_none" title="none"> <a style="color:blue" title="34389732" target="_blank" href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=34389732&dopt=Abstract"> PubMed </a> </span> </span> <OnlyViewableByAuthor><div class="ratings"> <div class="journal-subject">Folyóirat szakterülete: Scopus - Oncology&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Pharmacology (medical)&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> <div class="journal-subject">Folyóirat szakterülete: Scopus - Radiology, Nuclear Medicine and Imaging&nbsp;&nbsp;&nbsp;SJR indikátor:&nbsp;D1</div> </div></OnlyViewableByAuthor> <div class="publication-citation" style="margin-left: 0.5cm;"> <span title="Nyilvános idézőközlemények összesen, említések nélkül" class="citingPub-count">Nyilvános idéző összesen: 18</span> | Független: 16 | Függő: 2 | Nem jelölt: 0 | WoS jelölt: 15 | Scopus jelölt:&nbsp;16 | WoS/Scopus jelölt:&nbsp;18 | DOI jelölt:&nbsp;18 </div> <div class="publication-citation"> <a target="_blank" href="/api/publication?cond=citations.related;eq;32165251&sort=publishedYear,desc&sort=title"> Idézett közlemények száma: 2 </a> </div> <div class="mtid"><span class="long-pub-mtid">Közlemény: 32165251</span> | <span class="status-data status-VALIDATED"> Egyeztetett </span> Forrás Idéző | <span class="type-subtype">Folyóiratcikk ( Szakcikk ) </span> | <span class="pub-category">Tudományos</span> | <span class="publication-sourceOfData">Scopus</span> </div> <div class="lastModified">Utolsó módosítás: 2023.10.18. 08:43 Szalóky-Siki Ágnes (SE_KK_Admin5_SZSA, admin) </div> <pre class="comment" style="margin-top: 0; margin-bottom: 0;"><u>Megjegyzés</u>: Department of Oncology, Johns Hopkins University School of Medicine and the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins, Baltimore, MD, United States Department of Medicine, University of Maryland, Baltimore, MD, United States Department of Dermatology, Emory School of Medicine, Atlanta Veterans Administration Medical Center, Atlant...</pre> </div></div>