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- CD44 regulates epigenetic plasticity by mediating iron endocytosis
CD44 regulates epigenetic plasticity by mediating iron endocytosis
Authors
Sebastian Müller, Fabien Sindikubwabo, Tatiana Cañeque, Anne Lafon, Antoine Versini, Bérangère Lombard, Damarys Loew, Adeline Durand, Céline Vallot, Sylvain Baulande, Nicolas Servant, Raphaël Rodriguez
Abstract
SUMMARY
CD44 is a transmembrane glycoprotein that is linked to various biological processes reliant on the epigenetic plasticity of cells, including development, inflammation, immune responses, wound healing and cancer progression. While thoroughly studied, functional regulatory roles of this so-called ‘cell surface marker’ remain elusive. Here, we report the discovery that CD44 mediates endocytosis of iron interacting with hyaluronates in tumorigenic cell lines and primary cancer cells. We found that this glycan-mediated iron endocytosis mechanism is enhanced during epithelial-mesenchymal transition, unlike the canonical transferrin-dependent pathway. This transition is further characterized by molecular changes required for iron-catalyzed oxidative demethylation of the repressive histone mark H3K9me2 that governs the expression of mesenchymal genes.
Members

RAPHAEL RODRIGUEZ
Directeur de recherche CNRS
CELINE VALLOT
Directeur de recherche CNRS
ADELINE LABLANCHE
Ingénieur de recherche
FABIEN SINDIKUBWABO
Chargé de recherche CNRS
SEBASTIAN MULLER
Chargé de recherche Inserm