A protective role for HIF-1 in response to redox manipulation and glucose deprivation: Implications for tumorigenesis

Kaye J. Williams, Brian A. Telfer, Rachel E. Airley, Hans P W Peters, Mary R. Sheridan, Albert J. Van der Kogel, Adrian L. Harris, Ian J. Stratford

    Research output: Contribution to journalArticlepeer-review


    We have investigated the role of HIF-1 in the cellular response to redox modulation via the inhibition of oxidative phosphorylation. We demonstrate that manipulation of redox in air, achieved by inhibiting cytochrome oxidase with cyanide, induces HIF-1 mediated transcription in wild-type CHO and HT1080 human tumour cells but not in CHO cells deficient in the oxygen responsive, HIF-1α sub-unit of HIF-1. Hypoglycaemia attenuates cyanide-mediated transcription in non-transformed HIF-1 wild-type CHO cells but not the human tumour derived cell line. Cells lacking either HIF-1α, or the second composite sub-unit of HIF-1, HIF-1β, were markedly more sensitive to the combined stress of perturbed redox and hypoglycaemia than wild-type cells. As such conditions together with hypoxia are prevalent in tumours, these data suggest that HIF-1 may have a protective role in adaptation to the tumour microenvironment. In support of this we demonstrate that HIF-1α deficient cells are less tumorigenic than wild-type cells. They showed a reduced growth rate when grown as xenografts in nude mice. This was not related to vascular parameters that were identical to those found in HIF-1 wild-type tumours. The HIF-1 deficient tumours lacked focal expression of Glut-1 in hypoxic tumour regions. Compromized glucose uptake and metabolic adaptation to the tumour micro-environment may form the basis of the reduced tumorigenecity associated with these cells.
    Original languageEnglish
    Pages (from-to)282-290
    Number of pages8
    Issue number2
    Publication statusPublished - 10 Jan 2002


    • Cyanide
    • Glucose
    • Glut-1
    • HIF-1
    • Redox
    • Tumorigenesis


    Dive into the research topics of 'A protective role for HIF-1 in response to redox manipulation and glucose deprivation: Implications for tumorigenesis'. Together they form a unique fingerprint.

    Cite this