{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,19]],"date-time":"2026-05-19T05:09:25Z","timestamp":1779167365730,"version":"3.51.4"},"reference-count":51,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T00:00:00Z","timestamp":1778803200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100010355","name":"Hellenic Society of Medical Oncology","doi-asserted-by":"crossref","award":["2022"],"award-info":[{"award-number":["2022"]}],"id":[{"id":"10.13039\/501100010355","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Hellenic Society for Molecular Medicine and Personalized Diagnostics and Treatment"},{"name":"National Recovery and Resilience Plan \u201cGreece 2.0\u201d\u2014Next Generation EU","award":["5173820"],"award-info":[{"award-number":["5173820"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>TRAF3 (TNF Receptor Associated Factor 3) is a regulator of NF-\u03baB signaling, acting mainly as an inhibitor of the alternative NF-\u03baB pathway. While TRAF3 has a well-established role in immune function, mainly via B- and T-lymphocyte regulation, its roles in cancer remain unclear. Breast cancer is the most common malignancy in women and a neoplasm displaying high levels of intratumoral heterogeneity. Identifying and understanding key molecules at the interface of breast cancer cells and the immune system is crucial for advancing therapeutic strategies for breast cancer patients. Here, by employing publicly available breast cancer datasets, breast cancer cell lines stably expressing TRAF3, mass spectrometry analysis in combination with functional assays, co-culture systems, and signal pathway characterization, we sought to assess the specific role of TRAF3 in breast cancer cells and how TRAF3-expressing breast cancer cells affect their immune microenvironment. Our results indicate that TRAF3 protein overexpression inhibits colony formation through apoptosis regulation. Proteome analysis for TRAF3 interactors and over-representation analysis identified multiple protein complexes related to cell cycle, apoptosis, and immune responses. Furthermore, TRAF3-expressing breast cancer cells displayed reduced levels of PD-L1 and when co-cultured with PBMCs induced a pro-inflammatory profile with increased CD16-NK cells and higher levels of IFN-\u03b3 and TNF-\u03b1 and lower IL-10 and Tregs in the culture. These findings further expand the role of TRAF3 in breast cancer, not only as a regulator of EMT and survival of cancer cells, but also as a modulator of the tumor-immune microenvironment.<\/jats:p>","DOI":"10.3390\/ijms27104414","type":"journal-article","created":{"date-parts":[[2026,5,18]],"date-time":"2026-05-18T14:40:31Z","timestamp":1779115231000},"page":"4414","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Dual Role of Cancer Epithelial-Specific TRAF3 in Regulating Breast Cancer Cell Survival and Lymphocyte Activity"],"prefix":"10.3390","volume":"27","author":[{"given":"Chaido","family":"Sirinian","sequence":"first","affiliation":[{"name":"Molecular Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3152-4777","authenticated-orcid":false,"given":"Anne-Lise","family":"de Lastic","sequence":"additional","affiliation":[{"name":"Laboratory of Immunohematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Harry","family":"Zaverdas","sequence":"additional","affiliation":[{"name":"Department of Nursing, School of Health Rehabilitation Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Martha","family":"Nifora","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of West Attica, 12243 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dimitra","family":"Georgakopoulou","sequence":"additional","affiliation":[{"name":"Laboratory of Immunohematology, Department of Internal Medicine, Medical School, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9952-0636","authenticated-orcid":false,"given":"Martina","family":"Samiotaki","sequence":"additional","affiliation":[{"name":"Protein Chemistry Facility, Biomedical Sciences Research Center \u201cAlexander Fleming\u201d, 16672 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9944-2188","authenticated-orcid":false,"given":"Maria Ioanna","family":"Argentou","sequence":"additional","affiliation":[{"name":"Breast Unit, Department of Surgery, University Hospital of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stavros","family":"Peroukidis","sequence":"additional","affiliation":[{"name":"Panarkadikon General Hospital, 22100 Tripolis, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5409-045X","authenticated-orcid":false,"given":"S\u00f8ren E.","family":"Degn","sequence":"additional","affiliation":[{"name":"Department of Biomedicine, Aarhus University, 8000 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Maria","family":"Rusan","sequence":"additional","affiliation":[{"name":"Department of Molecular Medicine, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Pharmacology, Aarhus University Hospital, 8200 Aarhus, Denmark"},{"name":"Department of Clinical Medicine, Aarhus University, 8200 Aarhus, Denmark"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Konstantinos","family":"Theofilatos","sequence":"additional","affiliation":[{"name":"School of Cardiovascular and Metabolic Medicine & Sciences, King\u2019s College London, London SE1 7EH, UK"},{"name":"InSyBio PC, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Seferina","family":"Mavroudi","sequence":"additional","affiliation":[{"name":"Department of Nursing, School of Health Rehabilitation Sciences, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anastasios D.","family":"Papanastasiou","sequence":"additional","affiliation":[{"name":"Department of Biomedical Sciences, University of West Attica, 12243 Athens, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Angelos","family":"Koutras","sequence":"additional","affiliation":[{"name":"Molecular Oncology Laboratory, Division of Oncology, Department of Medicine, University of Patras, 26504 Patras, Greece"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,5,15]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"114822","DOI":"10.1016\/j.biopha.2023.114822","article-title":"The role of NF-\u03baB in breast cancer initiation, growth, metastasis, and resistance to chemotherapy","volume":"163","author":"Pavitra","year":"2023","journal-title":"Biomed. 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