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Claudin 1 inhibits cell migration and increases intercellular adhesion in triple-negative breast cancer cell line

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Abstract

Triple-negative “claudin 1 low” subtype represents around 15% of breast cancer and displays poor prognosis. The loss of claudin 1 is correlated with increased invasiveness and higher recurrence of the disease. Claudin 1 constitutes the backbone of the tight junction and is involved in cell-cell adhesion and migration processes. However, studies showed a controversial role of claudin 1 in cell migration. In this study, we aimed to clarify the effect of claudin 1 on migration of mesenchymal triple-negative breast cancer cells (TNBC). We reported that transient over expression of claudin 1 in MDA-MB-231 and Hs578T “claudin 1 low” TNBC cells inhibited cell migration using wound healing and transwell migration assays. In order to investigate more specifically the involvement of claudin 1, we generated stable MDA-MB-231 clones overexpressing claudin 1. Interestingly, the level of claudin 1 was correlated to the inhibition of cell migration and to the increase of cell-cell aggregation associated with enhanced formation of β-catenin adherens junction and occludin tight junction. Finally, we reported for the first time the key role of claudin 1 in the inhibition of cell migration process associated with the disappearance of stress fibers. These data suggest that re-expression of claudin 1 could be a promising strategy for regulating the migration of TNBC which no longer express claudin 1.

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Abbreviations

CLDN1:

Claudin 1

TJ:

Tight junction

EMT:

Epithelial–mesenchymal transition

MSL:

Mesenchymal-stem-like

DOCK:

Dedicator of cytokinesis

AJ:

Adherent junction

ZO-1:

Zonula occludens-1

TNBC:

Triple negative breast cancer

FCS:

Fetal calf serum

PDZ-domain-binding-motif:

PSD95, DlgA, ZO-1 domain binding motif

CSRP2:

Cysteine-rich-protein 2

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Acknowledgements

We thank Prof. S.N. Thornton for reviewing the English.

Funding

This work was supported by grants of the “Université de Lorraine”, the “Conseil Régional du Grand Est” and the “Ligue Contre le Cancer”. Marine Geoffroy was recipient of a PhD grant of the « Ministère de l’Enseignement Supérieur et de la Recherche ».

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Authors and Affiliations

  1. Université de Lorraine, CRAN, UMR 7039, 54506, Vandoeuvre-lès-Nancy, France

    Marine Geoffroy, Alexandra Kleinclauss, Sandra Kuntz & Isabelle Grillier-Vuissoz

  2. CNRS, CRAN, UMR 7039, 54506, Vandoeuvre-lès-Nancy, France

    Marine Geoffroy, Alexandra Kleinclauss, Sandra Kuntz & Isabelle Grillier-Vuissoz

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  1. Marine Geoffroy
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  2. Alexandra Kleinclauss
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MG, SK, IGV designed the study. MG, AK, SK performed the experiments. MG, SK, IGV analyzed the data and wrote the paper. All author reviewed the manuscript.

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Correspondence to Sandra Kuntz.

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Geoffroy, M., Kleinclauss, A., Kuntz, S. et al. Claudin 1 inhibits cell migration and increases intercellular adhesion in triple-negative breast cancer cell line. Mol Biol Rep 47, 7643–7653 (2020). https://doi.org/10.1007/s11033-020-05835-3

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