The pleiotropic effects of TNF? in breast cancer subtypes is regulated by TNFAIP3/A20

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dc.authorid0000-0002-1423-0435
dc.contributor.authorLee, Eunmi
dc.contributor.authorOuzounova, Maria
dc.contributor.authorPiranlıoğlu, Raziye
dc.contributor.authorMa, Minh Thu
dc.contributor.authorGüzel, Mustafa
dc.contributor.authorMarasco, Daniela
dc.contributor.authorChadli, Ahmed
dc.contributor.authorGestwicki, Jason E.
dc.contributor.authorCowell, John Kenneth
dc.contributor.authorWicha, Max S.
dc.contributor.authorHassan, Khaled A.
dc.contributor.authorKorkaya, Hasan
dc.date.accessioned10.07.201910:49:13
dc.date.accessioned2019-07-10T19:49:44Z
dc.date.available10.07.201910:49:13
dc.date.available2019-07-10T19:49:44Z
dc.date.issued2019
dc.departmentİstanbul Medipol Üniversitesi, Rektörlük, Rejeneratif ve Restoratif Tıp Araştırmaları Merkezi (REMER)
dc.departmentİstanbul Medipol Üniversitesi, Uluslararası Tıp Fakültesi, Dahili Tıp Bilimleri Bölümü, Tıbbi Farmakoloji Ana Bilim Dalı
dc.descriptionWOS: 000456589800002
dc.descriptionPubMed ID: 30166590
dc.description.abstractTNF alpha is a pleiotropic cytokine which fuels tumor cell growth, invasion, and metastasis in some malignancies, while in others it induces cytotoxic cell death. However, the molecular mechanism by which TNF alpha exerts its diverse effects on breast cancer subtypes remains elusive. Using in vitro assays and mouse xenografts, we show here that TNF alpha contributes to the aggressive properties of triple negative breast cancer (TNBC) cell lines via upregulation of TNFAIP3(A20). In a striking contrast, TNF alpha induces a potent cytotoxic cell death in luminal (ER+) breast cancer cell lines which fail to upregulate A20 expression. Overexpression of A20 not only protects luminal breast cancer cell lines from TNF alpha-induced cell death via inducing HSP70-mediated anti-apoptotic pathway but also promotes a robust EMT/CSC phenotype by activating the pStat3-mediated inflammatory signaling. Furthermore, A20 overexpression in luminal breast cancer cells induces aggressive metastatic properties in mouse xenografts via generating a permissive inflammatory microenvironment constituted by granulocytic-MDSCs. Collectively, our results reveal a mechanism by which A20 mediates pleiotropic effects of TNF alpha playing role in aggressive behaviors of TNBC subtype while its deficiency results in TNF alpha-induced apoptotic cell death in luminal breast cancer subtype.
dc.description.sponsorshipNCI NIH HHS [R35 CA197585]en_US
dc.identifier.citationLee, E., Ouzounova, M., Piranlıoğlu, R., Ma, M. T., Güzel, M., Marasco, D. … Korkaya, H. (2019). The pleiotropic effects of TNF? in breast cancer subtypes is regulated by TNFAIP3/A20. Oncogene, 38(4), 469-482. https://dx.doi.org/10.1038/s41388-018-0472-0
dc.identifier.doi10.1038/s41388-018-0472-0
dc.identifier.endpage482
dc.identifier.issn0950-9232
dc.identifier.issn1476-5594
dc.identifier.issue4
dc.identifier.scopusqualityQ1
dc.identifier.startpage469
dc.identifier.urihttps://dx.doi.org/10.1038/s41388-018-0472-0
dc.identifier.urihttps://hdl.handle.net/20.500.12511/1744
dc.identifier.volume38
dc.identifier.wosqualityQ1
dc.indekslendigikaynakWeb of Science
dc.indekslendigikaynakScopus
dc.indekslendigikaynakPubMed
dc.language.isoen
dc.publisherNature Publishing Group
dc.relation.ispartofOncogeneen_US
dc.relation.publicationcategoryMakale - Uluslararası Hakemli Dergi - Kurum Öğretim Elemanı
dc.rightsinfo:eu-repo/semantics/openAccess
dc.subjectBreast Cancer
dc.subjectTNFAIP3/A20
dc.subjectTNF?
dc.titleThe pleiotropic effects of TNF? in breast cancer subtypes is regulated by TNFAIP3/A20
dc.typeArticle

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