HIF-1 mediates metabolic responses to intratumoral hypoxia and oncogenic mutations

Hypoxia occurs frequently in human cancers and induces adaptive changes in cell metabolism that include a switch from oxidative phosphorylation to glycolysis, increased glycogen synthesis, and a switch from glucose to glutamine as the major substrate for fatty acid synthesis. This broad metabolic reprogramming is coordinated at the transcriptional level by HIF-1, which functions as a master regulator to balance oxygen supply and demand. HIF-1 is also activated in cancer cells by tumor suppressor (e.g., VHL) loss of function and oncogene gain of function (leading to PI3K/AKT/mTOR activity) and mediates metabolic alterations that drive cancer progression and resistance to therapy. Inhibitors of HIF-1 or…

• UD
  U.S. Department of Defense

  Awards: W81XWH, W81XWH-12-1-0464
• AC
  American Cancer Society
• JH
  Johns Hopkins University
• NI
  National Institutes of Health

  Awards: CA143868, W81XWH