| First Author | Cantelmo AR | Year | 2016 |
| Journal | Cancer Cell | Volume | 30 |
| Issue | 6 | Pages | 968-985 |
| PubMed ID | 27866851 | Mgi Jnum | J:237983 |
| Mgi Id | MGI:5817825 | Doi | 10.1016/j.ccell.2016.10.006 |
| Citation | Cantelmo AR, et al. (2016) Inhibition of the Glycolytic Activator PFKFB3 in Endothelium Induces Tumor Vessel Normalization, Impairs Metastasis, and Improves Chemotherapy. Cancer Cell 30(6):968-985 |
| abstractText | 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-kappaB signaling. PFKFB3-blockade treatment also improved chemotherapy of primary and metastatic tumors. |
