HIF-1-regulated glucose metabolism: a key to apoptosis resistance?
Resistance of human cancers to current treatment regimens remains a challenge in oncology. Therefore, there has been much interest in identifying molecular pathways that are responsible for primary or acquired resistance of cancers. Hypoxia is a characteristic feature of most solid tumors and has been associated with poor treatment response. In response to hypoxia cancer cells undergo a variety of adoptive changes including activation of signaling pathways, which promote cancer cell survival and block cell death. Hypoxia inducible factor-1 (HIF-1) is the major transcription factor that mediates adaptation of cancer cells to the hypoxic environment. There is mounting evidence that Hif-1alpha, the oxygen sensitive subunit of HIF-1, provides protection against cell death and stimulates tumor growth by upregulating genes that are involved in cellular energy metabolism. Thus, Hif-1alpha and hypoxia-inducible genes represent attractive targets for the development of pharmacological inhibitors, which may offer new therapeutic options for a wide range of adult and also pediatric malignancies.
Fulda
Simone
S
University Children's Hospital, Ulm, Germany. simone.fulda@uniklinik-ulm.de
Debatin
Klaus-Michael
KM
D000222:Adaptation, Physiological / Q000187:drug effects / Q000502:physiology; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology*; D015687:Cell Hypoxia / Q000187:drug effects / Q000502:physiology*; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism*
C497442:HIF1A protein, human; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D005947:Glucose