Article Dans Une Revue Cancer Cell Année : 2016

Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy

Résumé

Abnormal tumor vessels promote metastasis and impair chemotherapy. Hence, tumor vessel normalization (TVN) is emerging as an anti-cancer treatment. Here, we show that tumor endothelial cells (ECs) have a hyper-glycolytic metabolism, shunting intermediates to nucleotide synthesis. EC haplo-deficiency or blockade of the glycolytic activator PFKFB3 did not affect tumor growth, but reduced cancer cell invasion, intravasation, and metastasis by normalizing tumor vessels, which improved vessel maturation and perfusion. Mechanistically, PFKFB3 inhibition tightened the vascular barrier by reducing VE-cadherin endocytosis in ECs, and rendering pericytes more quiescent and adhesive (via upregulation of N-cadherin) through glycolysis reduction; it also lowered the expression of cancer cell adhesion molecules in ECs by decreasing NF-κB signaling. PFKFB3-blockade treatment also improved chemotherapy of primary and metastatic tumors.

Fichier sous embargo
Fichier sous embargo
Date de visibilité indéterminée

Dates et versions

inserm-05170152 , version 1 (18-07-2025)

Licence

Identifiants

Citer

Anna Rita Cantelmo, Lena-Christin Conradi, Aleksandra Brajic, Jermaine Goveia, Joanna Kalucka, et al.. Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy. Cancer Cell, 2016, 30 (6), pp.968 - 985. ⟨10.1016/j.ccell.2016.10.006⟩. ⟨inserm-05170152⟩

Collections

44 Consultations
1 Téléchargements

Altmetric

Partager

  • More