Chemokine receptor CXCR4 downregulated by von Hippel–Lindau tumour suppressor pVHL

Peter Staller, Jitka Sulitkova, Joanna Lisztwan, Holger Moch, Edward J. Oakeley and Wilhelm Krek ()
Additional contact information
Peter Staller: Friedrich Miescher Institute for Biomedical Research
Jitka Sulitkova: Friedrich Miescher Institute for Biomedical Research
Joanna Lisztwan: Friedrich Miescher Institute for Biomedical Research
Holger Moch: University of Basel
Edward J. Oakeley: Friedrich Miescher Institute for Biomedical Research
Wilhelm Krek: Friedrich Miescher Institute for Biomedical Research

Nature, 2003, vol. 425, issue 6955, 307-311

Abstract: Abstract Organ-specific metastasis is governed, in part, by interactions between chemokine receptors on cancer cells and matching chemokines in target organs. For example, malignant breast cancer cells express the chemokine receptor CXCR4 and commonly metastasize to organs that are an abundant source of the CXCR4-specific ligand stromal cell-derived factor-1α (ref. 1). It is still uncertain how an evolving tumour cell is reprogrammed to express CXCR4, thus implementing the tendency to metastasize to specific organs. Here we show that the von Hippel–Lindau tumour suppressor protein pVHL negatively regulates CXCR4 expression owing to its capacity to target hypoxia-inducible factor (HIF) for degradation under normoxic conditions. This process is suppressed under hypoxic conditions, resulting in HIF-dependent CXCR4 activation. An analysis of clear cell renal carcinoma that manifests mutation of the VHL gene in most cases revealed an association of strong CXCR4 expression with poor tumour-specific survival. These results suggest a mechanism for CXCR4 activation during tumour cell evolution and imply that VHL inactivation acquired by incipient tumour cells early in tumorigenesis confers not only a selective survival advantage but also the tendency to home to selected organs.

Date: 2003
References: Add references at CitEc
Citations: View citations in EconPapers (1)

Downloads: (external link)
https://www.nature.com/articles/nature01874 Abstract (text/html)
Access to the full text of the articles in this series is restricted.

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:nature:v:425:y:2003:i:6955:d:10.1038_nature01874

Ordering information: This journal article can be ordered from
https://www.nature.com/

DOI: 10.1038/nature01874

Access Statistics for this article

Nature is currently edited by Magdalena Skipper

More articles in Nature from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().