{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,11]],"date-time":"2026-05-11T23:25:49Z","timestamp":1778541949749,"version":"3.51.4"},"reference-count":67,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T00:00:00Z","timestamp":1654214400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Oncol."],"abstract":"<jats:p>Estrogen receptors (ERs) have pivotal roles in the development and progression of triple-negative breast cancer (TNBC). Interactions among cancer cells and tumor microenvironment are orchestrated by the extracellular matrix that is rapidly emerging as prominent contributor of fundamental processes of breast cancer progression. Early studies have correlated ER\u03b2 expression in tumor sites with a more aggressive clinical outcome, however ER\u03b2 exact role in the progression of TNBC remains to be elucidated. Herein, we introduce the functional role of ER\u03b2 suppression following isolation of monoclonal cell populations of MDA-MB-231 breast cancer cells transfected with shRNA against human <jats:italic>ESR2<\/jats:italic> that permanently resulted in 90% reduction of ER\u03b2 mRNA and protein levels. Further, we demonstrate that clone selection results in strongly reduced levels of the aggressive functional properties of MDA-MB-231 cells, by transforming their morphological characteristics, eliminating the mesenchymal-like traits of triple-negative breast cancer cells. Monoclonal populations of shER\u03b2 MDA-MB-231 cells undergo universal matrix reorganization and pass on a mesenchymal-to-epithelial transition state. These striking changes are encompassed by the total prevention of tumorigenesis <jats:italic>in vivo<\/jats:italic> following ER\u03b2 maximum suppression and isolation of monoclonal cell populations in TNBC cells. We propose that these novel findings highlight the promising role of ER\u03b2 targeting in future pharmaceutical approaches for managing the metastatic dynamics of TNBC breast cancer.<\/jats:p>","DOI":"10.3389\/fonc.2022.917633","type":"journal-article","created":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T06:59:25Z","timestamp":1654239565000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":12,"title":["ESR2 Drives Mesenchymal-to-Epithelial Transition in Triple-Negative Breast Cancer and Tumorigenesis In Vivo"],"prefix":"10.3389","volume":"12","author":[{"given":"Zoi","family":"Piperigkou","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasios","family":"Koutsandreas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marco","family":"Franchi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Vasiliki","family":"Zolota","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitrios","family":"Kletsas","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alberto","family":"Passi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nikos K.","family":"Karamanos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1965","published-online":{"date-parts":[[2022,6,3]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.CD-21-1059","article-title":"Hallmarks of Cancer: New Dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discovery"},{"key":"B2","doi-asserted-by":"publisher","first-page":"597","DOI":"10.1038\/nrc3093","article-title":"The Different Roles of ER Subtypes in Cancer Biology and Therapy","volume":"11","author":"Thomas","year":"2011","journal-title":"Nat Rev Cancer"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.07.006","article-title":"Estrogen Receptor-Mediated Targeting of the Extracellular Matrix Network in Cancer","volume":"62","author":"Piperigkou","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15776","article-title":"A Guide to the Composition and Functions of the Extracellular Matrix","volume":"288","author":"Karamanos","year":"2021","journal-title":"FEBS J"},{"key":"B5","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.matbio.2018.08.007","article-title":"Matrix Modeling and Remodeling: A Biological Interplay Regulating Tissue Homeostasis and Diseases","author":"Karamanos","year":"2019","journal-title":"Matrix Biol"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1111\/febs.14818","article-title":"The Extracellular Matrix as a Multitasking Player in Disease","volume":"286","author":"Theocharis","year":"2019","journal-title":"FEBS J"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.3390\/cancers13061441","article-title":"Key Matrix Remodeling Enzymes: Functions and Targeting in Cancer","volume":"13","author":"Piperigkou","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2021.07.009","article-title":"Extracellular Matrix-Based Cancer Targeting","volume":"27","author":"Karamanos","year":"2021","journal-title":"Trends Mol Med"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1021\/acs.chemrev.8b00354","article-title":"Proteoglycan Chemical Diversity Drives Multifunctional Cell Regulation and Therapeutics","volume":"118","author":"Karamanos","year":"2018","journal-title":"Chem Rev"},{"key":"B10","doi-asserted-by":"publisher","first-page":"61","DOI":"10.1038\/nature11412","article-title":"Comprehensive Molecular Portraits of Human Breast Tumours","volume":"490","author":"Yan","year":"2012","journal-title":"Nature"},{"key":"B11","doi-asserted-by":"publisher","first-page":"69","DOI":"10.1038\/s41467-021-27734-2","article-title":"C\/EBPB-Dependent Adaptation to Palmitic Acid Promotes Tumor Formation in Hormone Receptor Negative Breast Cancer","volume":"13","author":"Liu","year":"2022","journal-title":"Nat Commun"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.93.12.5925","article-title":"Cloning of a Novel Receptor Expressed in Rat Prostate and Ovary","volume":"93","author":"Kuiper","year":"1996","journal-title":"Proc Natl Acad Sci"},{"key":"B13","doi-asserted-by":"publisher","first-page":"2255","DOI":"10.3390\/cells9102256","article-title":"Egfr\/Er\u03b2-Mediated Cell Morphology and Invasion Capacity Are Associated With Matrix Culture Substrates in Breast Cancer","volume":"9","author":"Kyriakopoulou","year":"2020","journal-title":"Cells"},{"key":"B14","doi-asserted-by":"publisher","first-page":"4","DOI":"10.1016\/j.matbio.2016.05.003","article-title":"Estrogen Receptor Beta Modulates Breast Cancer Cells Functional Properties, Signaling and Expression of Matrix Molecules","volume":"56","author":"Piperigkou","year":"2016","journal-title":"Matrix Biol"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/febs.16240","article-title":"EGFR is a Pivotal Player of the E2\/Er\u03b2 \u2013 Mediated Functional Properties, Aggressiveness, and Stemness in Triple-Negative Breast Cancer Cells","volume":"289","author":"Kyriakopoulou","year":"2021","journal-title":"FEBS J"},{"key":"B16","doi-asserted-by":"publisher","first-page":"89","DOI":"10.1038\/s41580-021-00442-x","article-title":"The Many Regulators of Epithelial\u2013Mesenchymal Transition","volume":"23","author":"Bracken","year":"2022","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00452","article-title":"Mechanistic Pathways of Malignancy in Breast Cancer Stem Cells","volume":"10","author":"Yousefnia","year":"2020","journal-title":"Front Oncol"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2020.00280","article-title":"DCST1-AS1 Promotes TGF-\u03b2-Induced Epithelial\u2013Mesenchymal Transition and Enhances Chemoresistance in Triple-Negative Breast Cancer Cells via ANXA1","volume":"10","author":"Tang","year":"2020","journal-title":"Front Oncol"},{"key":"B19","doi-asserted-by":"publisher","first-page":"94","DOI":"10.1016\/j.matbio.2017.08.002","article-title":"Estrogen Receptor Beta as Epigenetic Mediator of miR-10b and miR-145 in Mammary Cancer","volume":"64","author":"Piperigkou","year":"2017","journal-title":"Matrix Biol"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2020.100024","article-title":"miR-200b Restrains EMT and Aggressiveness and Regulates Matrix Composition Depending on ER Status and Signaling in Mammary Cancer","author":"Piperigkou","year":"2020","journal-title":"Matrix Biol Plus"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-020-05948-0","article-title":"Contrasting Activities of Estrogen Receptor Beta Isoforms in Triple Negative Breast Cancer","volume":"185","author":"Yan","year":"2021","journal-title":"Breast Cancer Res Treat"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.3390\/cancers12061477","article-title":"Insights Into the Role of Estrogen Receptor \u03b2 in Triple-Negative Breast Cancer","volume":"12","author":"Sellitto","year":"2020","journal-title":"Cancers (Basel)"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1007\/BF00300234","article-title":"Determination of Subcutaneous Tumor Size in Athymic (Nude) Mice","volume":"24","author":"Tomayko","year":"1989","journal-title":"Cancer Chemother Pharmacol"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1387\/ijdb.092948ow","article-title":"Modeling and Quantification of Cancer Cell Invasion Through Collagen Type I Matrices","volume":"54","author":"de Wever","year":"2010","journal-title":"Int J Dev Biol"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/0471142735.im0728s37","article-title":"Measurement of Cellular Adhesion Under Static Conditions","volume":"37","author":"Mobley","year":"2000","journal-title":"Curr Protoc Immunol"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkz430","article-title":"GEPIA2: An Enhanced Web Server for Large-Scale Expression Profiling and Interactive Analysis","volume":"47","author":"Tang","year":"2019","journal-title":"Nucleic Acids Res"},{"key":"B27","doi-asserted-by":"publisher","first-page":"56","DOI":"10.1016\/j.semcancer.2017.08.010","article-title":"Prognostic and Predictive Biomarkers in Breast Cancer: Past, Present and Future","volume":"52","author":"Nicolini","year":"2018","journal-title":"Semin Cancer Biol"},{"key":"B28","doi-asserted-by":"publisher","first-page":"2","DOI":"10.1016\/j.steroids.2017.11.005","article-title":"Communication Between Genomic and non-Genomic Signaling Events Coordinate Steroid Hormone Actions","volume":"133","author":"Wilkenfeld","year":"2018","journal-title":"Steroids"},{"key":"B29","doi-asserted-by":"publisher","first-page":"99","DOI":"10.1016\/j.cellsig.2018.07.010","article-title":"Advances in Targeting Epidermal Growth Factor Receptor Signaling Pathway in Mammary Cancer","volume":"51","author":"Kyriakopoulou","year":"2018","journal-title":"Cell Signalling"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1007\/s10549-012-2289-9","article-title":"Role of Epidermal Growth Factor Receptor in Breast Cancer","volume":"136","author":"Masuda","year":"2012","journal-title":"Breast Cancer Res Treat"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/srep40138","article-title":"IGF-IR Cooperates With Er\u03b1 to Inhibit Breast Cancer Cell Aggressiveness by Regulating the Expression and Localisation of ECM Molecules","volume":"7","author":"Afratis","year":"2017","journal-title":"Sci Rep"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2021.650453","article-title":"Extracellular Matrix: Emerging Roles and Potential Therapeutic Targets for Breast Cancer","volume":"11","author":"Zhao","year":"2021","journal-title":"Front Oncol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1016\/j.copbio.2016.02.007","article-title":"Impact of the Physical Microenvironment on Tumor Progression and Metastasis","volume":"40","author":"Spill","year":"2016","journal-title":"Curr Opin Biotechnol"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1159\/000348415","article-title":"Computational Model to Probe Cellular Mechanics During Epithelial-Mesenchymal Transition","volume":"197","author":"Vargas","year":"2013","journal-title":"Cells Tissues Organs"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.3390\/cells9092031","article-title":"Extracellular Matrix-Mediated Breast Cancer Cells Morphological Alterations, Invasiveness, and Microvesicles\/Exosomes Release","volume":"9","author":"Franchi","year":"2020","journal-title":"Cells"},{"key":"B36","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1038\/s41598-021-03984-4","article-title":"Quantifying the Cell Morphology and Predicting Biological Behavior of Signet Ring Cell Carcinoma Using Deep Learning","volume":"12","author":"Da","year":"2022","journal-title":"Sci Rep"},{"key":"B37","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1016\/j.molmed.2008.03.004","article-title":"Epithelial\u2013mesenchymal Transition and the Invasive Potential of Tumors","volume":"14","author":"Gavert","year":"2008","journal-title":"Trends Mol Med"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.21841","article-title":"Matrix Metalloproteinase MMP9 Maintains Epithelial Barrier Function and Preserves Mucosal Lining in Colitis Associated Cancer","volume":"8","author":"Pujada","year":"2017","journal-title":"Oncotarget"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-14-609","article-title":"MMP-9 Expression Varies According to Molecular Subtypes of Breast Cancer","volume":"14","author":"Yousef","year":"2014","journal-title":"BMC Cancer"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2007.07.012","article-title":"Adherens and Tight Junctions: Structure, Function and Connections to the Actin Cytoskeleton","volume":"1778","author":"Hartsock","year":"2008","journal-title":"Biochim Biophys Acta (BBA)"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1038\/onc.2013.118","article-title":"Mammary Epithelial Cell Interactions With Fibronectin Stimulate Epithelial-Mesenchymal Transition","volume":"33","author":"Park","year":"2014","journal-title":"Oncogene"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0008726","article-title":"Impact of Tumor Cell Cytoskeleton Organization on Invasiveness and Migration: A Microchannel-Based Approach","volume":"5","author":"Rolli","year":"2010","journal-title":"PLos One"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.ccr.2012.02.022","article-title":"Accessories to the Crime: Functions of Cells Recruited to the Tumor Microenvironment","volume":"21","author":"Hanahan","year":"2012","journal-title":"Cancer Cell"},{"key":"B44","doi-asserted-by":"publisher","first-page":"59","DOI":"10.1186\/s12964-020-0530-4","article-title":"Tumor Microenvironment Complexity and Therapeutic Implications at a Glance","volume":"18","author":"Baghban","year":"2020","journal-title":"Cell Communication Signaling"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/nrc.2017.6","article-title":"Pre-Metastatic Niches: Organ-Specific Homes for Metastases","volume":"17","author":"Peinado","year":"2017","journal-title":"Nat Rev Cancer"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1002\/iub.2608","article-title":"Hyaluronan as \u201cAgent Smith\u201d in Cancer Extracellular Matrix Pathobiology: Regulatory Roles in Immune Response, Cancer Progression and Targeting","author":"Kokoretsis","year":"2022","journal-title":"IUBMB Life"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2020.100038","article-title":"Complexity of Matrix Phenotypes","author":"Iozzo","year":"2020","journal-title":"Matrix Biol Plus"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1016\/j.matbio.2017.10.008","article-title":"Proteoglycans Remodeling in Cancer: Underlying Molecular Mechanisms","author":"Theocharis","year":"2019","journal-title":"Matrix Biol"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.26089","article-title":"Estrogen Receptor-Beta is a Potential Target for Triple Negative Breast Cancer Treatment","volume":"9","author":"Austin","year":"2018","journal-title":"Oncotarget"},{"key":"B50","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1155\/2015\/925703","article-title":"Biologic Roles of Estrogen Receptor-\u03b2 and Insulin-Like Growth Factor-2 in Triple-Negative Breast Cancer","volume":"2015","author":"Hamilton","year":"2015","journal-title":"BioMed Res Int"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1002\/1878-0261.12377","article-title":"Targeting Newly Identified Er\u03b2\/TGF-\u03b21\/SMAD3 Signals With the FDA-Approved Anti-Estrogen Faslodex or an Er\u03b2 Selective Antagonist in Renal Cell Carcinoma","volume":"12","author":"Song","year":"2018","journal-title":"Mol Oncol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/cancers11121826","article-title":"Molecular Targeting Therapy Against EGFR Family in Breast Cancer: Progress and Future Potentials","volume":"11","author":"Maennling","year":"2019","journal-title":"Cancers (Basel)"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00041.2022","article-title":"The microRNA-Cell Surface Proteoglycan Axis in Cancer Progression","volume":"322","author":"Piperigkou","year":"2022","journal-title":"Am J Physiol-Cell Physiol"},{"key":"B54","doi-asserted-by":"publisher","first-page":"713","DOI":"10.3390\/cancers13040713","article-title":"Epigenetic Alterations in Triple-Negative Breast Cancer\u2014the Critical Role of Extracellular Matrix","volume":"13","author":"Zolota","year":"2021","journal-title":"Cancers (Basel)"},{"key":"B55","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-09-4104","article-title":"Estrogen Receptor \u03b21 Expression Is Regulated by miR-92 in Breast Cancer","volume":"70","author":"Al-Nakhle","year":"2010","journal-title":"Cancer Res"},{"key":"B56","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1016\/j.semcancer.2019.09.004","article-title":"Emerging Roles of ECM Remodeling Processes in Cancer","volume":"62","author":"Mohan","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"B57","doi-asserted-by":"publisher","DOI":"10.3389\/fgene.2021.809600","article-title":"Landscape Analysis of Matrix Metalloproteinases Unveils Key Prognostic Markers for Patients With Breast Cancer","volume":"12","author":"Cheng","year":"2022","journal-title":"Front Genet"},{"key":"B58","doi-asserted-by":"publisher","DOI":"10.2741\/4364","article-title":"Matrix Metalloproteinases as Drivers and Therapeutic Targets in Breast Cancer","volume":"20","author":"Radisky","year":"2015","journal-title":"Front Biosci"},{"key":"B59","doi-asserted-by":"publisher","first-page":"149","DOI":"10.1186\/s12885-021-07860-2","article-title":"Prognostic Values of Tumoral MMP2 and MMP9 Overexpression in Breast Cancer: A Systematic Review and Meta-Analysis","volume":"21","author":"Jiang","year":"2021","journal-title":"BMC Cancer"},{"key":"B60","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1486806","article-title":"Cadherins in Development: Cell Adhesion, Sorting, and Tissue Morphogenesis","volume":"20","author":"Halbleib","year":"2006","journal-title":"Genes Dev"},{"key":"B61","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1699","article-title":"Regulation of Cadherin-Mediated Adhesion in Morphogenesis","volume":"6","author":"Gumbiner","year":"2005","journal-title":"Nat Rev Mol Cell Biol"},{"key":"B62","doi-asserted-by":"crossref","DOI":"10.1007\/978-3-319-28140-7_19","article-title":"\u201cFibronectin.,\u201d","volume-title":"Angiogenesis in Health, Disease and Malignancy","author":"Salajegheh","year":"2016"},{"key":"B63","doi-asserted-by":"publisher","DOI":"10.1016\/S1534-5807(02)00216-2","article-title":"Spatio-Temporal Regulation of Rac1 Localization and Lamellipodia Dynamics During Epithelial Cell-Cell Adhesion","volume":"3","author":"Ehrlich","year":"2002","journal-title":"Dev Cell"},{"key":"B64","doi-asserted-by":"publisher","DOI":"10.1016\/j.mbplus.2020.100026","article-title":"Long Filopodia and Tunneling Nanotubes Define New Phenotypes of Breast Cancer Cells in 3D Cultures","author":"Franchi","year":"2020","journal-title":"Matrix Biol Plus"},{"key":"B65","doi-asserted-by":"publisher","DOI":"10.1016\/j.semcancer.2019.08.003","article-title":"Epithelial-To-Mesenchymal Transition and Invadopodia Markers in Breast Cancer: Lumican a Key Regulator","volume":"62","author":"Karamanou","year":"2020","journal-title":"Semin Cancer Biol"},{"key":"B66","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamcr.2006.07.001","article-title":"Regulation of the Actin Cytoskeleton in Cancer Cell Migration and Invasion","volume":"1773","author":"Yamaguchi","year":"2007","journal-title":"Biochim Biophys Acta (BBA)"},{"key":"B67","doi-asserted-by":"publisher","first-page":"2980","DOI":"10.1038\/s41467-018-05367-2","article-title":"The Actin Cytoskeletal Architecture of Estrogen Receptor Positive Breast Cancer Cells Suppresses Invasion","volume":"9","author":"Padilla-Rodriguez","year":"2018","journal-title":"Nat Commun"}],"container-title":["Frontiers in Oncology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.917633\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,3]],"date-time":"2022-06-03T06:59:28Z","timestamp":1654239568000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fonc.2022.917633\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,6,3]]},"references-count":67,"alternative-id":["10.3389\/fonc.2022.917633"],"URL":"https:\/\/doi.org\/10.3389\/fonc.2022.917633","relation":{},"ISSN":["2234-943X"],"issn-type":[{"value":"2234-943X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,6,3]]},"article-number":"917633"}}