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Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells

Oncogene volume 30, pages 2514–2525 (2011)Cite this article

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Abstract

MUC1 is a transmembrane glycoprotein which is typically expressed at the apical membrane of normal epithelial cells. In cancer cells, the over-expression of MUC1 and its aberrant localization around the cell membrane and in the cytoplasm favours its interaction with different protein partners such as epidermal growth factor receptor (EGFR) and can promote tumour proliferation through the activation of oncogenic signalling pathways. Our aims were to study the mechanisms inducing MUC1 cytoplasmic localization in pancreatic cancer cells, and to decipher their impact on EGFR cellular localization and activation. Our results showed that galectin-3, an endogenous lectin, is co-expressed with MUC1 in human pancreatic ductal adenocarcinoma, and that it favours the endocytosis of MUC1 and EGFR. Depletion of galectin-3 by RNA interference increased the interaction between MUC1 and EGFR, EGFR and ERK-1,2 phosphorylation, and translocation of EGFR to the nucleus. On the contrary, silencing of galectin-3 led to a decrease of cyclin-D1 levels and of cell proliferation. The galectin-3-dependent regulation of MUC1/EGFR functions may represent an interesting mechanism modulating the EGFR-stimulated cell growth of pancreatic cancer cells.

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Acknowledgements

We acknowledge expert support provided by D Trinel, N Jouy and M Figeac. We thank Professor N Porchet and MP Ducourouble for their constant support; G Grard, E Crème, MH Gevaert, R Siminsky, M Samyn and V Dumetz for their technical assistance. J Merlin is a recipient of a PhD fellowship from the Université de Lille 2 and Région Nord-Pas de Calais. This work was supported by a grant from the Comité du Nord de la Ligue Nationale contre le Cancer (to PP). This work was supported by a grant from the french Ligue Nationale contre le Cancer (comité du Nord).

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Authors and Affiliations

  1. INSERM, U837, Equipe 5, ‘Mucines, Différenciation et cancérogenèse épithéliales’, Place de Verdun, Lille Cedex, France

    J Merlin, L Stechly, S de Beaucé, E Leteurtre, I van Seuningen, G Huet & P Pigny

  2. Université de Lille 2, Centre de Recherche Jean-Pierre Aubert, Place de Verdun, Lille Cedex, France

    J Merlin, L Stechly, S de Beaucé, E Leteurtre, I van Seuningen, G Huet & P Pigny

  3. Laboratoire de Biochimie & Hormonologie, Centre de Biologie & Pathologie, CHRU, Lille Cedex, France

    L Stechly, G Huet & P Pigny

  4. Service d’anatomie-pathologique, Centre de Biologie & Pathologie, CHRU, Lille Cedex, France

    S de Beaucé & E Leteurtre

  5. Institut de Recherche Interdisciplinaire, USR3078 CNRS, Villeneuve d’Ascq, France

    D Monté

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Correspondence to P Pigny.

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Merlin, J., Stechly, L., de Beaucé, S. et al. Galectin-3 regulates MUC1 and EGFR cellular distribution and EGFR downstream pathways in pancreatic cancer cells. Oncogene 30, 2514–2525 (2011). https://doi.org/10.1038/onc.2010.631

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