Tumor cells also secrete vascular endothelial growth factor (VEGF) into the TME, resulting in the upregulation of 6-phosphofructo-2-kinase/fructose-2, 6-biphosphatase 3(PFKFB3) in endothelial cells, which activates PFK-1 to promote the glycolytic phenotype as well as proliferation (124). The gene discussed is PFKFB3; the disease is neoplasm.