{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:47:47Z","timestamp":1787028467386,"version":"build-2736575974"},"reference-count":72,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T00:00:00Z","timestamp":1640217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100000024","name":"Canadian Institutes of Health Research","doi-asserted-by":"publisher","award":["MOP-86634"],"award-info":[{"award-number":["MOP-86634"]}],"id":[{"id":"10.13039\/501100000024","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000038","name":"Natural Sciences and Engineering Research Council","doi-asserted-by":"publisher","award":["EGP 501325-16"],"award-info":[{"award-number":["EGP 501325-16"]}],"id":[{"id":"10.13039\/501100000038","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Erosive destruction of joint structures is a critical event in the progression of rheumatoid arthritis (RA), in which fibroblast-like synoviocytes (FLS) are the primary effectors. We previously reported that the ability of RA FLS to degrade extracellular matrix (ECM) components depends on the formation of actin-rich membrane protrusions, called invadosomes, through processes that remain elusive. 14-3-3\u03b7 belongs to a family of scaffolding proteins involved in a wide range of cellular functions, and its expression is closely related to joint damage and disease activity in RA patients. In this study, we sought to assess the role of 14-3-3\u03b7 in joint damage by examining its contribution to the invadosome formation phenotype of FLS. Using human primary FLS, we show that 14-3-3\u03b7 expression is closely associated with their ability to form invadosomes. Furthermore, knockdown of 14-3-3\u03b7 using shRNAs decreases the level of invadosome formation in RA FLS, whereas addition of the recombinant protein to FLS from healthy individuals promotes their formation. Mechanistic studies suggest that 14-3-3\u03b7 regulates invadosome formation by increasing Snail expression, a mechanism that involves nuclear exclusion of the transcription repressor FOXO3. Our results implicate the 14-3-3\u03b7\u2013FOXO3\u2013Snail axis in promoting the aggressive ECM-degrading phenotype of RA FLS, and suggest a role for this scaffolding protein in cartilage degradation.<\/jats:p>","DOI":"10.3390\/ijms23010123","type":"journal-article","created":{"date-parts":[[2021,12,23]],"date-time":"2021-12-23T10:16:18Z","timestamp":1640254578000},"page":"123","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":14,"title":["14-3-3\u03b7 Promotes Invadosome Formation via the FOXO3\u2013Snail Axis in Rheumatoid Arthritis Fibroblast-like Synoviocytes"],"prefix":"10.3390","volume":"23","author":[{"given":"Maleck","family":"Kadiri","sequence":"first","affiliation":[{"name":"Department of Immunology and Cell Biology, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Charbonneau","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Lalanne","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kelly","family":"Harper","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3369-7364","authenticated-orcid":false,"given":"Fr\u00e9d\u00e9ric","family":"Balg","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony","family":"Marotta","sequence":"additional","affiliation":[{"name":"Augurex Life Sciences Corp., Vancouver, BC V5T 4T5, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0751-2821","authenticated-orcid":false,"given":"Claire M.","family":"Dubois","sequence":"additional","affiliation":[{"name":"Department of Immunology and Cell Biology, Universit\u00e9 de Sherbrooke, Sherbrooke, QC J1H 5N4, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,23]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1016\/j.pop.2018.02.010","article-title":"Early Diagnosis and Treatment of Rheumatoid Arthritis","volume":"45","author":"Littlejohn","year":"2018","journal-title":"Prim. Care"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1580","DOI":"10.1136\/ard.2010.138461","article-title":"2010 Rheumatoid Arthritis Classification Criteria: An American College of Rheumatology\/European League Against Rheumatism Collaborative Initiative","volume":"69","author":"Aletaha","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"472","DOI":"10.1007\/s11926-012-0275-1","article-title":"Treatment Strategies in Early Rheumatoid Arthritis and Prevention of Rheumatoid Arthritis","volume":"14","author":"Demoruelle","year":"2012","journal-title":"Curr. Rheumatol. Rep."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"R99","DOI":"10.1186\/ar4547","article-title":"14-3-3\u03b7 Is a Novel Mediator Associated with the Pathogenesis of Rheumatoid Arthritis and Joint Damage","volume":"16","author":"Maksymowych","year":"2014","journal-title":"Arthritis Res. Ther."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"664","DOI":"10.1080\/14397595.2019.1637575","article-title":"14-3-3\u03b7 Protein in Serum and Synovial Fluid Correlates with Radiographic Damage and Progression in a Longitudinal Evaluation of Patients with Established Rheumatoid Arthritis","volume":"30","author":"Hammam","year":"2020","journal-title":"Mod. Rheumatol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1498","DOI":"10.3906\/sag-1812-137","article-title":"Importance of 14-3-3eta, Anti-CarP, and Anti-Sa in the Diagnosis of Seronegative Rheumatoid Arthritis","volume":"49","author":"Salman","year":"2019","journal-title":"Turk. J. Med. Sci."},{"key":"ref_7","first-page":"57","article-title":"Serum 14-3-3\u03b7 Could Improve the Diagnostic Rate of Rheumatoid Arthritis and Correlates to Disease Activity","volume":"49","author":"Guan","year":"2019","journal-title":"Ann. Clin. Lab. Sci."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.drudis.2015.09.012","article-title":"The Role of the 14-3-3 Protein Family in Health, Disease, and Drug Development","volume":"21","author":"Aghazadeh","year":"2016","journal-title":"Drug Discov. Today"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1016\/j.semcdb.2011.08.009","article-title":"14-3-3 Proteins: Diverse Functions in Cell Proliferation and Cancer Progression","volume":"22","author":"Freeman","year":"2011","journal-title":"Semin. Cell Dev. Biol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"384","DOI":"10.1007\/BF02339012","article-title":"Molecular Evolution of the 14-3-3 Protein Family","volume":"43","author":"Wang","year":"1996","journal-title":"J. Mol. Evol."},{"key":"ref_11","first-page":"1650","article-title":"Detection of High Levels of 2 Specific Isoforms of 14-3-3 Proteins in Synovial Fluid from Patients with Joint Inflammation","volume":"34","author":"Kilani","year":"2007","journal-title":"J. Rheumatol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"2104","DOI":"10.3899\/jrheum.131446","article-title":"Serum 14-3-3\u03b7 Is a Novel Marker That Complements Current Serological Measurements to Enhance Detection of Patients with Rheumatoid Arthritis","volume":"41","author":"Maksymowych","year":"2014","journal-title":"J. Rheumatol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1002\/art.1780391103","article-title":"Invasive Fibroblast-like Synoviocytes in Rheumatoid Arthritis. Passive Responders or Transformed Aggressors?","volume":"39","author":"Firestein","year":"1996","journal-title":"Arthritis Rheum."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1186\/s13317-020-00145-x","article-title":"Transformation of Fibroblast-like Synoviocytes in Rheumatoid Arthritis; from a Friend to Foe","volume":"12","author":"Mousavi","year":"2021","journal-title":"Autoimmun. Highlights"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1038\/nrrheum.2012.190","article-title":"Duality of Fibroblast-like Synoviocytes in RA: Passive Responders and Imprinted Aggressors","volume":"9","author":"Bottini","year":"2013","journal-title":"Nat. Rev. Rheumatol."},{"key":"ref_16","first-page":"w13529","article-title":"Fibroblasts as Therapeutic Targets in Rheumatoid Arthritis and Cancer","volume":"142","author":"Juarez","year":"2012","journal-title":"Swiss Med. Wkly"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1591","DOI":"10.1002\/art.30305","article-title":"Formation of Invadopodia-like Structures by Synovial Cells Promotes Cartilage Breakdown in Collagen-Induced Arthritis: Involvement of the Protein Tyrosine Kinase Src","volume":"63","author":"Lauzier","year":"2011","journal-title":"Arthritis Rheum."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/j.tcb.2017.03.003","article-title":"Tumor Cell Invadopodia: Invasive Protrusions That Orchestrate Metastasis","volume":"27","author":"Eddy","year":"2017","journal-title":"Trends Cell Biol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"359","DOI":"10.1016\/j.ajpath.2015.10.021","article-title":"Snail Is a Critical Mediator of Invadosome Formation and Joint Degradation in Arthritis","volume":"186","author":"Lauzier","year":"2016","journal-title":"Am. J. Pathol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"3264","DOI":"10.4049\/jimmunol.1500502","article-title":"Dubois CM Platelet-Derived Growth Factor Receptor Activation Promotes the Prodestructive Invadosome-Forming Phenotype of Synoviocytes from Patients with Rheumatoid Arthritis","volume":"196","author":"Charbonneau","year":"2016","journal-title":"J. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"R159","DOI":"10.1186\/ar3899","article-title":"Transglutaminase 2 Cross-Linking Activity Is Linked to Invadopodia Formation and Cartilage Breakdown in Arthritis","volume":"14","author":"Lauzier","year":"2012","journal-title":"Arthritis Res. Ther."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"479","DOI":"10.2217\/epi-2016-0151","article-title":"Epigenetic Alterations in Rheumatoid Arthritis Fibroblast-like Synoviocytes","volume":"9","author":"Doody","year":"2017","journal-title":"Epigenomics"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"145","DOI":"10.1016\/j.bcp.2019.03.018","article-title":"Regulation of Fibroblast-like Synoviocyte Transformation by Transcription Factors in Arthritic Diseases","volume":"165","author":"Bhattaram","year":"2019","journal-title":"Biochem. Pharmacol."},{"key":"ref_24","first-page":"461","article-title":"MiR-212-3p Reduced Proliferation, and Promoted Apoptosis of Fibroblast-like Synoviocytes via down-Regulating SOX5 in Rheumatoid Arthritis","volume":"22","author":"Liu","year":"2018","journal-title":"Eur. Rev. Med. Pharmacol. Sci."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"39","DOI":"10.1002\/art.38899","article-title":"Transcription Factor Snail Regulates Tumor Necrosis Factor \u03b1-Mediated Synovial Fibroblast Activation in the Rheumatoid Joint","volume":"67","author":"Chen","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"1763","DOI":"10.1136\/annrheumdis-2013-203610","article-title":"JNK-Dependent Downregulation of FoxO1 Is Required to Promote the Survival of Fibroblast-like Synoviocytes in Rheumatoid Arthritis","volume":"74","author":"Grabiec","year":"2015","journal-title":"Ann. Rheum. Dis."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1002\/art.37807","article-title":"Simvastatin Inhibits Cysteine-Rich Protein 61 Expression in Rheumatoid Arthritis Synovial Fibroblasts through the Regulation of Sirtuin-1\/FoxO3a Signaling","volume":"65","author":"Kok","year":"2013","journal-title":"Arthritis Rheum."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"482","DOI":"10.1016\/j.biocel.2009.10.013","article-title":"Forkhead Transcription Factors in Chronic Inflammation","volume":"42","author":"Peng","year":"2010","journal-title":"Int. J. Biochem. Cell Biol."},{"key":"ref_29","first-page":"925350","article-title":"FOXO Transcription Factors: Their Clinical Significance and Regulation","volume":"2014","author":"Wang","year":"2014","journal-title":"Biomed. Res. Int."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"2189","DOI":"10.1158\/0008-5472.CAN-12-3767","article-title":"FOXO3a Is a Major Target of Inactivation by PI3K\/AKT Signaling in Aggressive Neuroblastoma","volume":"73","author":"Santo","year":"2013","journal-title":"Cancer Res."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.canlet.2019.04.019","article-title":"FOXO3a Knockdown Promotes Radioresistance in Nasopharyngeal Carcinoma by Inducing Epithelial-Mesenchymal Transition and the Wnt\/\u03b2-Catenin Signaling Pathway","volume":"455","author":"Luo","year":"2019","journal-title":"Cancer Lett."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s10555-020-09883-w","article-title":"FOXO Transcription Factor Family in Cancer and Metastasis","volume":"39","author":"Jiramongkol","year":"2020","journal-title":"Cancer Metastasis Rev."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2629","DOI":"10.1002\/art.39760","article-title":"Association Between Genetic Variation in FOXO3 and Reductions in Inflammation and Disease Activity in Inflammatory Polyarthritis","volume":"68","author":"Viatte","year":"2016","journal-title":"Arthritis Rheumatol."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1016\/j.cell.2013.08.034","article-title":"Human SNP Links Differential Outcomes in Inflammatory and Infectious Disease to a FOXO3-Regulated Pathway","volume":"155","author":"Lee","year":"2013","journal-title":"Cell"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/s41374-018-0184-7","article-title":"FOXO3 Is Involved in the Tumor Necrosis Factor-Driven Inflammatory Response in Fibroblast-like Synoviocytes","volume":"99","author":"Brandstetter","year":"2019","journal-title":"Lab. Investig."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"857","DOI":"10.1016\/S0092-8674(00)80595-4","article-title":"Akt Promotes Cell Survival by Phosphorylating and Inhibiting a Forkhead Transcription Factor","volume":"96","author":"Brunet","year":"1999","journal-title":"Cell"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"817","DOI":"10.1083\/jcb.200112059","article-title":"14-3-3 Transits to the Nucleus and Participates in Dynamic Nucleocytoplasmic Transport","volume":"156","author":"Brunet","year":"2002","journal-title":"J. Cell Biol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6608","DOI":"10.18632\/oncotarget.14245","article-title":"Subcellular Localization of FOXO3a as a Potential Biomarker of Response to Combined Treatment with Inhibitors of PI3K and Autophagy in PIK3CA-Mutant Cancer Cells","volume":"8","author":"Kim","year":"2016","journal-title":"Oncotarget"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"703","DOI":"10.1016\/S0898-6568(00)00131-5","article-title":"14-3-3 Proteins: Regulation of Subcellular Localization by Molecular Interference","volume":"12","author":"Muslin","year":"2000","journal-title":"Cell. Signal."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.yexcr.2016.08.014","article-title":"14-3-3\u03b6 Promotes Lung Cancer Cell Invasion by Increasing the Snail Protein Expression through Atypical Protein Kinase C (APKC)\/NF-\u039aB Signaling","volume":"348","author":"Tong","year":"2016","journal-title":"Exp. Cell Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1002\/cam4.1950","article-title":"14-3-3\u03b6 Promotes Gliomas Cells Invasion by Regulating Snail through the PI3K\/AKT Signaling","volume":"8","author":"Li","year":"2019","journal-title":"Cancer Med."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Nakamura, R., Ishii, H., Endo, K., Hotta, A., Fujii, E., Miyazawa, K., and Saitoh, M. (2018). Reciprocal Expression of Slug and Snail in Human Oral Cancer Cells. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0199442"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1128\/MCB.02061-07","article-title":"Repression of PTEN Phosphatase by Snail1 Transcriptional Factor during Gamma Radiation-Induced Apoptosis","volume":"28","author":"Herranz","year":"2008","journal-title":"Mol. Cell. Biol."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"5587","DOI":"10.1038\/s41388-018-0348-3","article-title":"The Dynamic and Stress-Adaptive Signaling Hub of 14-3-3: Emerging Mechanisms of Regulation and Context-Dependent Protein\u2013Protein Interactions","volume":"37","author":"Pennington","year":"2018","journal-title":"Oncogene"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e541","DOI":"10.1016\/j.ddtec.2012.10.001","article-title":"Small Molecules Modulation of 14-3-3 Protein-Protein Interactions","volume":"10","author":"Mori","year":"2013","journal-title":"Drug Discov. Today Technol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"45193","DOI":"10.1074\/jbc.M105971200","article-title":"14-3-3 Proteins Mediate an Essential Anti-Apoptotic Signal*","volume":"276","author":"Masters","year":"2001","journal-title":"J. Biol. Chem."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1453","DOI":"10.1016\/j.bbamcr.2011.05.001","article-title":"Bimodal Regulation of FoxO3 by AKT and 14-3-3","volume":"1813","author":"Dobson","year":"2011","journal-title":"Biochim. Biophys. Acta"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"38","DOI":"10.1186\/s13046-019-1046-x","article-title":"Knockdown of FOXO3a Induces Epithelial-Mesenchymal Transition and Promotes Metastasis of Pancreatic Ductal Adenocarcinoma by Activation of the \u03b2-Catenin\/TCF4 Pathway through SPRY2","volume":"38","author":"Li","year":"2019","journal-title":"J. Exp. Clin. Cancer Res."},{"key":"ref_49","doi-asserted-by":"crossref","unstructured":"Khorrami, A., Sharif Bagheri, M., Tavallaei, M., and Gharechahi, J. (2017). The Functional Significance of 14-3-3 Proteins in Cancer: Focus on Lung Cancer. Horm. Mol. Biol. Clin. Investig., 32.","DOI":"10.1515\/hmbci-2017-0032"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1779","DOI":"10.1158\/1078-0432.CCR-13-1687","article-title":"Downregulation of FOXO3a Promotes Tumor Metastasis and Is Associated with Metastasis-Free Survival of Patients with Clear Cell Renal Cell Carcinoma","volume":"20","author":"Ni","year":"2014","journal-title":"Clin. Cancer Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"5654","DOI":"10.1158\/1078-0432.CCR-10-0376","article-title":"Foxo3a Suppression of Urothelial Cancer Invasiveness through Twist1, Y-Box\u2013Binding Protein 1, and E-Cadherin Regulation","volume":"16","author":"Shiota","year":"2010","journal-title":"Clin. Cancer Res."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Jacob, A., and Prekeris, R. (2015). The Regulation of MMP Targeting to Invadopodia during Cancer Metastasis. Front. Cell Dev. Biol., 3.","DOI":"10.3389\/fcell.2015.00004"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"19597","DOI":"10.18632\/aging.103919","article-title":"Characterization of the Expression and Prognostic Value of 14-3-3 Isoforms in Breast Cancer","volume":"12","author":"Mei","year":"2020","journal-title":"Aging"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"533","DOI":"10.1016\/j.canep.2012.05.003","article-title":"Expression of 14-3-3\u03b3 in Patients with Breast Cancer: Correlation with Clinicopathological Features and Prognosis","volume":"36","author":"Song","year":"2012","journal-title":"Cancer Epidemiol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1016\/j.neulet.2016.06.009","article-title":"Overexpression of the 14-3-3gamma Protein in Embryonic Mice Results in Neuronal Migration Delay in the Developing Cerebral Cortex","volume":"628","author":"Cornell","year":"2016","journal-title":"Neurosci. Lett."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"24","DOI":"10.1186\/s13075-020-2110-9","article-title":"Tumour Necrosis Factor Alpha Promotes Secretion of 14-3-3\u03b7 by Inducing Necroptosis in Macrophages","volume":"22","author":"Trimova","year":"2020","journal-title":"Arthritis Res. Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"74","DOI":"10.1002\/art.38878","article-title":"Expression and Function of Aminopeptidase N\/CD13 Produced by Fibroblast Like Synoviocytes in Rheumatoid Arthritis: Role of CD13 in Chemotaxis of Cytokine Activated T Cells Independent of Enzymatic Activity","volume":"67","author":"Morgan","year":"2015","journal-title":"Arthritis Rheumatol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1016\/j.cellsig.2016.12.007","article-title":"Extracellular Functions of 14-3-3 Adaptor Proteins","volume":"31","author":"Kaplan","year":"2017","journal-title":"Cell. Signal."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"2180","DOI":"10.1002\/art.22653","article-title":"Inhibition of Forkhead Box Class O Family Member Transcription Factors in Rheumatoid Synovial Tissue","volume":"56","author":"Ludikhuize","year":"2007","journal-title":"Arthritis Rheum."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1136\/ard.2009.109991","article-title":"FoxO3a Involved in Neutrophil and T Cell Survival Is Overexpressed in Rheumatoid Blood and Synovial Tissue","volume":"69","author":"Tournadre","year":"2010","journal-title":"Ann. Rheum. Dis."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"2867","DOI":"10.3892\/ol.2017.5851","article-title":"Phosphorylation and Acetylation Modifications of FOXO3a: Independently or Synergistically?","volume":"13","author":"Wang","year":"2017","journal-title":"Oncol. Lett."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1038\/cgt.2016.15","article-title":"14-3-3\u03b6 Silencing Retards Tongue Squamous Cell Carcinoma Progression by Inhibiting Cell Survival and Migration","volume":"23","author":"Jin","year":"2016","journal-title":"Cancer Gene Ther."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Aljabal, G., and Yap, B.K. (2020). 14-3-3\u03c3 and Its Modulators in Cancer. Pharmaceuticals, 13.","DOI":"10.3390\/ph13120441"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"226","DOI":"10.1016\/j.tips.2021.01.001","article-title":"14-3-3 Proteins: Novel Pharmacological Targets in Neurodegenerative Diseases","volume":"42","author":"Pair","year":"2021","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1703","DOI":"10.18632\/oncotarget.13786","article-title":"FOXO1 Inhibits the Invasion and Metastasis of Hepatocellular Carcinoma by Reversing ZEB2-Induced Epithelial-Mesenchymal Transition","volume":"8","author":"Dong","year":"2016","journal-title":"Oncotarget"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"R21","DOI":"10.1186\/bcr1872","article-title":"Forkhead Box Transcription Factor FOXO3a Suppresses Estrogen-Dependent Breast Cancer Cell Proliferation and Tumorigenesis","volume":"10","author":"Zou","year":"2008","journal-title":"Breast Cancer Res."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"7410","DOI":"10.1038\/sj.onc.1209086","article-title":"FOXO Transcription Factors at the Interface between Longevity and Tumor Suppression","volume":"24","author":"Greer","year":"2005","journal-title":"Oncogene"},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"42110","DOI":"10.18632\/oncotarget.9881","article-title":"Pharmacological Activation of FOXO3 Suppresses Triple-Negative Breast Cancer in Vitro and in Vivo","volume":"7","author":"Park","year":"2016","journal-title":"Oncotarget"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1016\/j.ccr.2009.03.017","article-title":"Translational Activation of Snail1 and Other Developmentally Regulated Transcription Factors by YB-1 Promotes an Epithelial-Mesenchymal Transition","volume":"15","author":"Evdokimova","year":"2009","journal-title":"Cancer Cell"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"777","DOI":"10.1038\/s41388-020-01562-y","article-title":"FOXO3a-Driven MiRNA Signatures Suppresses VEGF-A\/NRP1 Signaling and Breast Cancer Metastasis","volume":"40","author":"Song","year":"2021","journal-title":"Oncogene"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"12433","DOI":"10.18632\/oncotarget.14015","article-title":"MicroRNAs as Regulators and Mediators of Forkhead Box Transcription Factors Function in Human Cancers","volume":"8","author":"Li","year":"2016","journal-title":"Oncotarget"},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"4256","DOI":"10.4161\/cc.10.24.18552","article-title":"MiR-34 and SNAIL Form a Double-Negative Feedback Loop to Regulate Epithelial-Mesenchymal Transitions","volume":"10","author":"Siemens","year":"2011","journal-title":"Cell Cycle"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/123\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T07:51:46Z","timestamp":1760169106000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/1\/123"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,12,23]]},"references-count":72,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2022,1]]}},"alternative-id":["ijms23010123"],"URL":"https:\/\/doi.org\/10.3390\/ijms23010123","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,12,23]]}}}