Article (Scientific journals)
Zonula occludens-1/NF-κB/CXCL8: a new regulatory axis for tumor angiogenesis.
Lesage, Julien; Suarez-Carmona, Meggy; Neyrinck-Leglantier, Deborah et al.
2017In FASEB Journal, 31 (4), p. 1678-1688
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Keywords :
EMT; IL-8; ZO-1; tumor progression
Abstract :
[en] 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.
Disciplines :
Oncology
Author, co-author :
Lesage, Julien
Suarez-Carmona, Meggy ;  Université de Liège
Neyrinck-Leglantier, Deborah
Grelet, Simon
Blacher, Silvia ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Hunziker, Walter
Birembaut, Philippe
Noël, Agnès ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Nawrocki-Raby, Béatrice
Gilles, Christine  ;  Université de Liège > Département des sciences cliniques > Labo de biologie des tumeurs et du développement
Polette, Myriam 
 These authors have contributed equally to this work.
Language :
English
Title :
Zonula occludens-1/NF-κB/CXCL8: a new regulatory axis for tumor angiogenesis.
Publication date :
April 2017
Journal title :
FASEB Journal
ISSN :
0892-6638
eISSN :
1530-6860
Publisher :
Federation of American Society for Experimental Biology, Bethesda, United States - Maryland
Volume :
31
Issue :
4
Pages :
1678-1688
Peer reviewed :
Peer Reviewed verified by ORBi
Available on ORBi :
since 03 February 2017

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