Figure 2.

Angiogenesis in tumors is closely associated with EC metabolism. Glucose is the main energy resource of any cell. Glucose enters the EC cell through GLUT transporters (glucose transporters). Expression of GLUT transporters are up-regulated under hypoxic condition. Monocarboxylate transporter 1(MCT1), a transporter for lactate is highly expressed in cancers including breast. Hypoxia and acidic tumor environment turn “ON” the angiogenic switch. Under hypoxic condition OxPhos flux is reduced and the cells shift to a more aerobic glycolysis; as a result the pH of the cytoplasm becomes more acidic. Acidosis contributes to more robust expression of HIF-1α expression and increased IL8/VEGF signaling contributes to upregulation of glycolytic enzymes especially 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 3 (PFKFB3). PFKFB3 is essential for EC motility and sprouting. Two important biomolecules required for EC proliferation are glutamine and fatty acid (FA). FA entry into the mitochondria is facilitated via carnitine palmitoyl transferase 1A (CPT1A). FA oxidation is essential for nucleic acid synthesis and hence essential for EC proliferation. Glutamine is essential for redox homeostasis and biomass synthesis. In tumorigenesis, glutamine metabolism is up-regulated to compensate the energy requirement which was compromised due to reduced oxidative phosphor relation (OxPhos) flux [26,29,31,35,36,37].