Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • News & Views
  • Published:

Targeting tumors through the HIF system

Hypoxia-inducible factor (HIF) is a key transcriptional regulator of the cellular response to hypoxia that is upregulated in many common cancers. Blockade of the pathway may provide a new opportunity for the development of cancer therapeutics (pages 1335-1340).

This is a preview of subscription content, access via your institution

Relevant articles

Open Access articles citing this article.

Access options

Buy this article

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Multiple steps in the activation of the HIF transcriptional response provide potential points for therapeutic manipulation.

Steve Horwitz

References

  1. Kung, A.L., Wang, S., Klco, J.M., Kaelin, W.G. & Livingston, D.M. Suppression of tumor growth through disruption of hypoxia-inducible transcription. Nature Med. 6, 1335–1340 (2000).

    Article  CAS  Google Scholar 

  2. Semenza, G.L. & Wang, G.L. A nuclear factor induced by hypoxia via de novo protein synthesis binds to the human erythropoietin gene enhancer at a site required for transcriptional activation. Mol. Cell. Biol. 12, 5447–5454 (1992).

    Article  CAS  Google Scholar 

  3. Maxwell, P.H., Pugh, C.W. & Ratcliffe, P.J. Inducible operation of the erythropoietin 3′ enhancer in multiple cell lines: evidence for a widespread oxygen sensing mechanism. Proc. Natl. Acad. Sci. USA 90, 2423–2427 (1993).

    Article  CAS  Google Scholar 

  4. Semenza, G. HIF-1 and human disease: one highly involved factor. Genes Dev. 14, 1983–1991 (2000).

    CAS  PubMed  Google Scholar 

  5. Höckel, M. et al. Association between tumor hypoxia and malignant progression in advanced cancer of the uterine cervix. Cancer Res. 56, 4509–4515 (1996).

    PubMed  Google Scholar 

  6. Maxwell, P.H. et al. HIF-1 modulates gene expression in solid tumors and influences both angiogenesis and tumor growth. Proc. Natl. Acad. Sci. USA 94, 8104–8109 (1997).

    Article  CAS  Google Scholar 

  7. Ryan, H.E., Lo, J. & Johnson, R.S. HIF-1α is required for solid tumor formation and embryonic vascularization. EMBO J. 17, 3005–3015 (1998).

    Article  CAS  Google Scholar 

  8. Carmeliet, P. et al. Role of HIF-1α in hypoxia-mediated apoptosis, cell proliferation and tumour angiogenesis. Nature 394, 485–490 (1998).

    Article  CAS  Google Scholar 

  9. Wenger, R.H. Mammalian oxygen sensing, signalling and gene regulation. J. Exp. Biol. 203, 1253–1263 (2000).

    CAS  PubMed  Google Scholar 

  10. Bhattacharya, S. et al. Functional role of p35srj, a novel p300/CBP-binding protein, during transactivation by HIF-1. Genes Dev. 13, 64–75 (1999).

    Article  CAS  Google Scholar 

  11. Zhong, H. et al. Overexpression of HIF-1α in common human cancers and their metastases. Cancer Res. 59, 5830–5835 (1999).

    CAS  PubMed  Google Scholar 

  12. Bruick, R.K. Expression of the gene encoding the proapoptotic Nip3 protein is induced by hypoxia. Proc. Natl. Acad. Sci. USA 97, 9082–9087 (2000).

    Article  CAS  Google Scholar 

  13. Maxwell, P.H. et al. The tumour suppressor protein VHL targets hypoxia-inducible factors for oxygen-dependent proteolysis. Nature 399, 271–275 (1999).

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ratcliffe, P., Pugh, C. & Maxwell, P. Targeting tumors through the HIF system. Nat Med 6, 1315–1316 (2000). https://doi.org/10.1038/82113

Download citation

  • Issue Date:

  • DOI: https://doi.org/10.1038/82113

This article is cited by

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing