Sortilin limits EGFR signaling by promoting its internalization in lung cancer

Abstract : Tyrosine kinase receptors such as the epidermal growth factor receptor (EGFR) transduce information from the microenvironment into the cell and activate homeostatic signaling pathways. Internalization and degradation of EGFR after ligand binding limits the intensity of proliferative signaling, thereby helping to maintain cell integrity. In cancer cells, deregulation of EGFR trafficking has a variety of effects on tumor progression. Here we report that sortilin is a key regulator of EGFR internalization. Loss of sortilin in tumor cells promoted cell proliferation by sustaining EGFR signaling at the cell surface, ultimately accelerating tumor growth. In lung cancer patients, sortilin expression decreased with increased pathologic grade, and expression of sortilin was strongly correlated with survival, especially in patients with high EGFR expression. Sortilin is therefore a regulator of EGFR intracellular trafficking that promotes receptor internalization and limits signaling, which in turn impacts tumor growth.
Type de document :
Article dans une revue
Liste complète des métadonnées

Littérature citée [65 références]  Voir  Masquer  Télécharger
Contributeur : Philippe Sindou <>
Soumis le : mercredi 30 mai 2018 - 10:15:35
Dernière modification le : lundi 6 janvier 2020 - 12:18:48
Archivage à long terme le : vendredi 31 août 2018 - 13:48:08


Fichiers éditeurs autorisés sur une archive ouverte




Hussein Al Akhrass, Thomas Naves, François Vincent, Amandine Magnaudeix, Karine Durand, et al.. Sortilin limits EGFR signaling by promoting its internalization in lung cancer. Nature Communications, Nature Publishing Group, 2017, 8 (1), pp.1182. ⟨10.1038/s41467-017-01172-5⟩. ⟨hal-01803149⟩



Consultations de la notice


Téléchargements de fichiers