Metastasis-suppressor NME1 controls the invasive switch of breast cancer by regulating MT1-MMP surface clearance - Archive ouverte HAL Access content directly
Journal Articles Oncogene Year : 2021

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

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

Abstract

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.
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Dates and versions

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

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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⟩
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