The real face of HIF1α in the tumor process

It is well known that the hypoxia-inducible factor 1 alpha (HIF1 alpha) is detectable as adaptive metabolic response to hypoxia. However, HIF1/HIF1 alpha 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, HIF1 alpha 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 HIF1 alpha is a sensitive controller of the intracellular pH value independently of the oxygen concentration. Moreover, HIF1 alpha 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, HIF1 alpha 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.