Academic Journal
Zonula occludens-1/NF-κB/CXCL8: a new regulatory axis for tumor angiogenesis.
| العنوان: | Zonula occludens-1/NF-κB/CXCL8: a new regulatory axis for tumor angiogenesis. |
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| المؤلفون: | Lesage, Julien, Suarez-Carmona, Meggy, Neyrinck-Leglantier, Deborah, Grelet, Simon, Blacher, Silvia, Hunziker, Walter, Birembaut, Philippe, Noël, Agnès, Nawrocki-Raby, Béatrice, Gilles, Christine, Polette, Myriam |
| المصدر: | FASEB Journal, 31 (4), 1678-1688 (2017-04) |
| بيانات النشر: | Federation of American Society for Experimental Biology, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | EMT, IL-8, ZO-1, tumor progression, Human health sciences, Oncology, Sciences de la santé humaine, Oncologie |
| الوصف: | Zonula occludens-1 (ZO-1) is a submembrane scaffolding protein that may display proinvasive functions when it relocates from tight junctions into the cytonuclear compartment. This article examines the functional involvement of ZO-1 in CXCL8/IL-8 chemokine expression in lung and breast tumor cells. ZO-1 small interfering RNA and cDNA transfection experiments emphasized regulation of CXCL8/IL-8 expression via a cytonuclear pool of ZO-1. Luciferase reporter assays highlighted a 173-bp region of CXCL8/IL-8 promoter that responded to ZO-1. Moreover, by using mutated promoter constructs, we identified a NF-κB site as critical in this activation. Furthermore, NF-κB pathway signaling analysis revealed both IκBα and p65 phosphorylation in ZO-1-overexpressing cells, and subsequent p65 silencing validated its requirement for CXCL8/IL-8 induction. Investigation of the functional implication of this regulatory axis next showed the proangiogenic activity of ZO-1 in both ex vivo and in vivo angiogenesis assays. Finally, we found that non-small-cell lung carcinoma that presented a cytonuclear ZO-1 pattern was significantly more angiogenic that that without detectable cytonuclear ZO-1 expression. Taken together, our results demonstrate that ZO-1 regulates CXCL8/IL-8 expression via the NF-κB signaling pathway and its p65 subunit, which subsequently modulates the transcription of IL-8. We also provide evidence of a newly identified regulatory pathway that could promote angiogenesis. Thus, our results support the concept that the ZO-1 shuttle from the cell junction to the cytonuclear compartment may affect both the intrinsic invasive properties of tumor cells and the establishment of the protumoral microenvironment. |
| نوع الوثيقة: | journal article http://purl.org/coar/resource_type/c_6501 article peer reviewed |
| اللغة: | English |
| Relation: | urn:issn:0892-6638; urn:issn:1530-6860 |
| DOI: | 10.1096/fj.201600890R |
| URL الوصول: | https://orbi.uliege.be/handle/2268/206762 |
| Rights: | restricted access http://purl.org/coar/access_right/c_16ec info:eu-repo/semantics/restrictedAccess |
| رقم الانضمام: | edsorb.206762 |
| قاعدة البيانات: | ORBi |
| DOI: | 10.1096/fj.201600890R |
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