title: The real face of HIF1α in the tumor process.
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.
authors.affiliation: Department of Oral and Maxillofacial Plastic Surgery, Martin Luther University Halle-Wittenberg, Halle, Germany. matthias.kappler@medizin.uni-halle.de
authors.forename: Matthias
authors.initials: M
authors.lastname: Kappler
authors.forename: Helge
authors.initials: H
authors.lastname: Taubert
authors.forename: Johannes
authors.initials: J
authors.lastname: Schubert
authors.forename: Dirk
authors.initials: D
authors.lastname: Vordermark
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Eckert
mesh_terms: D000641:Ammonia / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D018698:Glutamic Acid / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009369:Neoplasms / Q000378:metabolism* / Q000473:pathology; D000644:Quaternary Ammonium Compounds / Q000378:metabolism
chemical_list: D051272:Glucose Transporter Type 1; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D000644:Quaternary Ammonium Compounds; D005973:Glutamine; D018698:Glutamic Acid; D000641:Ammonia