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miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers

Oncogene volume 29, pages 4436–4448 (2010)Cite this article

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A Retraction to this article was published on 14 December 2015

Abstract

Epithelial to mesenchymal transition (EMT) is a key step toward metastasis. MCF7 breast cancer cells conditionally expressing the EMT master regulator SNAI1 were used to identify early expressed microRNAs (miRNAs) and their targets that may contribute to the EMT process. Potential targets of miRNAs were identified by matching lists of in silico predicted targets and of inversely expressed mRNAs. MiRNAs were ranked based on the number of predicted hits, highlighting miR-661, a miRNA with so far no reported role in EMT. MiR-661 was found required for efficient invasion of breast cancer cells by destabilizing two of its predicted mRNA targets, the cell–cell adhesion protein Nectin-1 and the lipid transferase StarD10, resulting, in turn, in the downregulation of epithelial markers. Reexpression of Nectin-1 or StarD10 lacking the 3′-untranslated region counteracted SNAI1-induced invasion. Importantly, analysis of public transcriptomic data from a cohort of 295 well-characterized breast tumor specimen revealed that expression of StarD10 is highly associated with markers of luminal subtypes whereas its loss negatively correlated with the EMT-related, basal-like subtype. Collectively, our non-a priori approach revealed a nonpredicted link between SNAI1-triggered EMT and the down-regulation of Nectin-1 and StarD10 through the up-regulation of miR-661, which may contribute to the invasion of breast cancer cells and poor disease outcome.

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Acknowledgements

We thank M Yatskou, P Nazarov and A Muller (CRP-Santé, Luxembourg) for their help with the microarray data analysis. We thank C Hoffmann-Laporte (CRP-Santé, Luxembourg) for her help with confocal microscopy observations. We especially thank E Schaffner-Reckinger for critical reading of the article and P Savagner for helpful discussions. This work was supported by grants from the Fond National de la Recherche (FNR) du Luxembourg (BIOSAN), the Fondation Luxembourgeoise Contre le Cancer, Human Frontier Science Program (RGP0058/2005), INSERM and CNRS, France. A Saumet is a recipient of a fellowship from the Ministère de la Culture, de l’Enseignement Supérieur et de la Recherche, Luxembourg (BFR 08/046). M Moes and A Le Béchec are supported by AFR grants from the Fond National de la Recherche, Luxembourg.

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Authors and Affiliations

  1. Cytoskeleton and Cell Plasticity Lab, Life Sciences Research Unit–FSTC, University of Luxembourg, Luxembourg

    G Vetter, M Moes, A Le Béchec, C Laurini & E Friederich

  2. Institut de Recherche en Cancérologie de Montpellier, INSERM, U896, Montpellier, France

    A Saumet & C Theillet

  3. Microarray Center, Centre de Recherche Publique–Santé, Luxembourg

    L Vallar

  4. Hôpital Saint-Antoine, INSERM U938, Paris, France

    M Sabbah

  5. Sigma-Aldrich, Evry, France

    K Arar

  6. Institut de Génétique Moléculaire de Montpellier, CNRS, UMR 5535–IFR 122, Montpellier, France

    C-H Lecellier

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  1. G Vetter
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Correspondence to E Friederich.

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Vetter, G., Saumet, A., Moes, M. et al. miR-661 expression in SNAI1-induced epithelial to mesenchymal transition contributes to breast cancer cell invasion by targeting Nectin-1 and StarD10 messengers. Oncogene 29, 4436–4448 (2010). https://doi.org/10.1038/onc.2010.181

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