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Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells

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Abstract

During tumor invasion, tumor epithelial cells acquire migratory and invasive properties involving important phenotypic alterations. Among these changes, one can observe reorganization or a loss of cell–cell adhesion complexes such as tight junctions (TJs). TJs are composed of transmembrane proteins (occludin, claudins) linked to the actin cytoskeleton through cytoplasmic adaptor molecules including those of the zonula occludens family (ZO-1, -2, -3). We here evaluated the potential role of ZO-2 in the acquisition of invasive properties by tumor cells. In vivo, we showed a decrease of ZO-2 expression in bronchopulmonary cancers, with a preferential localization in the cytoplasm. In addition, in vitro, the localization of ZO-2 varied according to invasive properties of tumor cells, with a cytoplasmic localization correlating with invasion. In addition, we demonstrated that ZO-2 inhibition increases invasive and migrative capacities of invasive tumor cells. This was associated with an increase of MT1-MMP. These results suggest that ZO-2, besides its structural role in tight junction assembly, can act also as a repressor of tumor progression through its ability to reduce the expression of tumor-promoting genes in invasive tumor cells.

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Abbreviations

AC:

Adenocarcinomas

C/EBP:

CCAAT/enhancer-binding protein

CD1:

Cyclin D1

DMEM:

Dulbecco’s modified eagle’s medium

ECM:

Extracellular matrix

EGF:

Epidermal growth factor

HBECs:

Human bronchial epithelial cells

MMP:

Matrix metalloproteinase

MT1-MMP:

Membrane-type 1 MMP

NES:

Nuclear exporting signal

NLS:

Nuclear localization signal

SAF-B:

Scaffold attachment factor-B

SSC:

Squamous cell carcinomas

TAZ:

Transcriptional coactivator with PDZ-binding motif

TJ:

Tight junctions

YAP-2:

Yes kinase-associated protein 2

ZASP:

ZO-2 associated speckle protein

ZO-1:

Zonula occludens-1

ZO-2:

Zonula occludens-2

ZO-3:

Zonula occludens-3

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Acknowledgments

The research effort associated with this article was funded in part by the “Région Champagne-Ardenne”, the “Ligue Contre le Cancer”, the Lions’s Clubs of Soissons, Villers-Cotterets and Crépy en Valois, Un Euro contre le Cancer and the Fonds National pour la Santé ACI 2004-2010 INCa (Cancéropôle Grand-Est project), the Fonds de la Recherche Scientifique-FNRS (FRS-FNRS, Belgium), the “Partenariat Hubert Curien-Tournesol”.

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Authors and Affiliations

  1. INSERM UMR-S 903, SFR CAP-SANTE FED 4231, University of Reims-Champagne-Ardenne, 45, rue Cognacq-Jay, 51100, Reims, France

    E. Luczka, B. Nawrocki-Raby, C. Kileztky, P. Birembaut & Myriam Polette

  2. Laboratory of Developmental and Tumor Biology, GIGA-Cancer, University of Liège, Sart-Tilman, 4000, Liege, Belgium

    L. Syne & C. Gilles

  3. Epithelial Cell Biology Laboratory, Institute of Molecular and Cell Biology (IMCB), Singapore, 138673, Singapore

    W. Hunziker

  4. Laboratory of Histology, CHU of Reims, 45, rue Cognacq-Jay, 51100, Reims, France

    P. Birembaut & Myriam Polette

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  1. E. Luczka
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  2. L. Syne
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  3. B. Nawrocki-Raby
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  4. C. Kileztky
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  5. W. Hunziker
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  6. P. Birembaut
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  7. C. Gilles
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  8. Myriam Polette
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Correspondence to Myriam Polette.

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Luczka, E., Syne, L., Nawrocki-Raby, B. et al. Regulation of membrane-type 1 matrix metalloproteinase expression by zonula occludens-2 in human lung cancer cells. Clin Exp Metastasis 30, 833–843 (2013). https://doi.org/10.1007/s10585-013-9583-8

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  • DOI: https://doi.org/10.1007/s10585-013-9583-8

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