Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance - Institut Curie Accéder directement au contenu
Article Dans Une Revue Oncogene Année : 2021

Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance

Catalina Lodillinsky
Laetitia Fuhrmann
Olena Pylypenko
Xiao-Yan Li
  • Fonction : Auteur
Hélène Bonsang-Kitzis
  • Fonction : Auteur
Fabien Reyal
Sophie Vacher
  • Fonction : Auteur
Claire Calmel
  • Fonction : Auteur
Olivier de Wever
Ivan Bièche
  • Fonction : Auteur
Marie-Lise Lacombe
  • Fonction : Auteur
Ana Maria Eiján
Anne Vincent-Salomon
Stephen J Weiss
  • Fonction : Auteur
Mathieu Boissan

Résumé

Membrane Type 1 Matrix Metalloprotease (MT1-MMP) contributes to the invasive progression of breast cancers by degrading extracellular matrix tissues. Nucleoside diphosphate kinase, NME1/NM23-H1, has been identified as a metastasis suppressor; however, its contribution to local invasion in breast cancer is not known. Here, we report that NME1 is upregulated in ductal carcinoma in situ (DCIS) as compared to normal breast epithelial tissues. NME1 levels drop in microinvasive and invasive components of breast tumor cells relative to synchronous DCIS foci. We find a strong anticorrelation between NME1 and plasma membrane MT1-MMP levels in the invasive components of breast tumors, particularly in aggressive histological grade III and triple-negative breast cancers. Knockout of NME1 accelerates the invasive transition of breast tumors in the intraductal xenograft model. At the mechanistic level, we find that MT1-MMP, NME1 and dynamin-2, a GTPase known to require GTP production by NME1 for its membrane fission activity in the endocytic pathway, interact in clathrin-coated vesicles at the plasma membrane. Loss of NME1 function increases MT1-MMP surface levels by inhibiting endocytic clearance. As a consequence, the ECM degradation and invasive potentials of breast cancer cells are enhanced. This study identifies the down-modulation of NME1 as a potent driver of the in situ-to invasive transition during breast cancer progression.
Fichier principal
Vignette du fichier
94-nme1-mm1.mmp-Oncogene-Boissan-Jun21.pdf (10.99 Mo) Télécharger le fichier
Origine : Fichiers éditeurs autorisés sur une archive ouverte

Dates et versions

hal-03453132 , version 1 (27-11-2021)

Identifiants

Citer

Catalina Lodillinsky, Laetitia Fuhrmann, Marie Irondelle, Olena Pylypenko, Xiao-Yan Li, et al.. Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance. Oncogene, 2021, 40 (23), pp.4019 - 4032. ⟨10.1038/s41388-021-01826-1⟩. ⟨hal-03453132⟩
14 Consultations
18 Téléchargements

Altmetric

Partager

Gmail Facebook X LinkedIn More