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Nat Commun. 2017 Oct 30;8(1):1182. doi: 10.1038/s41467-017-01172-5.

Sortilin limits EGFR signaling by promoting its internalization in lung cancer.

Author information

1
EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr. Raymond Marcland, 87025, Limoges CEDEX, France.
2
EA3842 Homéostasie Cellulaire et Pathologies and Chaire de Pneumologie Expérimentale, Université de Limoges, Faculté de Médecine, 2 Rue du Dr. Raymond Marcland, 87025, Limoges CEDEX, France. thomas.naves@unilim.fr.
3
Service de Pathologie Respiratoire, Centre Hospitalier et Universitaire de Limoges, 87042, Limoges CEDEX, France.
4
Service d'Anatomie Pathologique, Centre Hospitalier et Universitaire de Limoges, 87042, Limoges CEDEX, France.
5
Service de Chirurgie Thoracique et Cardio-vasculaire, Centre Hospitalier et Universitaire de Limoges, 87042, Limoges CEDEX, France.
6
Service d'Immunologie, Centre Hospitalier et Universitaire de Limoges, 87042, Limoges CEDEX, France.

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.

PMID:
29084952
PMCID:
PMC5662760
DOI:
10.1038/s41467-017-01172-5
[Indexed for MEDLINE]
Free PMC Article

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