The real face of HIF1α in the tumor process

Cell Cycle. 2012 Nov 1;11(21):3932-6. doi: 10.4161/cc.21854. Epub 2012 Sep 17.

Abstract

It is well known that the hypoxia-inducible factor 1 α (HIF1α) is detectable as adaptive metabolic response to hypoxia. However, HIF1/HIF1α is detectable even under normoxic conditions, if the metabolism is altered, e.g., high proliferation index. Importantly, both hypoxic metabolism and the Warburg effect have in common a decrease of the intracellular pH value. In our interpretation, HIF1α is not directly accumulated by hypoxia, but by a process which occurs always under hypoxic conditions, a decrease of the intracellular pH value because of metabolic imbalances. We assume that HIF1α is a sensitive controller of the intracellular pH value independently of the oxygen concentration. Moreover, HIF1α has its major role in activating genes to eliminate toxic metabolic waste products (e.g., NH3/NH4+) generated by the tumor-specific metabolism called glutaminolysis, which occur during hypoxia, or the Warburg effect. For that reason, HIF1α appears as a potential target for tumor therapy to disturb the pH balance and to inhibit the elimination of toxic metabolic waste products in the tumor cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ammonia / metabolism
  • Glucose Transporter Type 1 / metabolism
  • Glutamic Acid / metabolism
  • Glutamine / metabolism
  • Humans
  • Hydrogen-Ion Concentration
  • Hypoxia-Inducible Factor 1, alpha Subunit / metabolism*
  • Neoplasms / metabolism*
  • Neoplasms / pathology
  • Quaternary Ammonium Compounds / metabolism

Substances

  • Glucose Transporter Type 1
  • Hypoxia-Inducible Factor 1, alpha Subunit
  • Quaternary Ammonium Compounds
  • Glutamine
  • Glutamic Acid
  • Ammonia