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Metastasis

One step closer

Nature Reviews Cancer volume 5, page 4 (2005)Cite this article

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Chemokines are a superfamily of small cytokine-like peptides involved in cell adhesion and migration. The expression of the CXC chemokine receptor 4 (CXCR4) and its natural ligand CXC chemokine ligand 12 (CXCL12) are known to be involved in breast cancer metastasis. As ERBB2 and CXCR4 can both be expressed in breast cancer cells, Hung and co-workers investigated whether there was a link between the two.

In human breast cancer cell lines, they showed that transgenic expression of ERBB2 leads to increased CXCR4 expression, most likely through an increased rate of translation of CXCR4 mRNA. Further in vitro studies demonstrated that blocking the activity of ERBB2 with the inhibitor trastuzumab (Herceptin), suppresses CXCR4 expression and blocks invasion mediated by CXCL12. Furthermore, inhibition of CXCR4 by a neutralizing antibody inhibits the migration and adhesion of ERBB2-expressing cells mediated by CXCL12. The authors also have evidence that degradation of CXCR4, once it has bound CXCL12, is reduced in ERBB2-expressing cells. This might be because ERBB2, by an unknown mechanism, reduces the ubiquitylation of CXCR4. In addition, studies in immunocompromised mice show that ERBB2-expressing breast cancer cells that no longer express significant levels of CXCR4, due to RNA interference, have a markedly reduced capacity to form lung metastases.

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References

ORIGINAL RESEARCH PAPER

  1. Li, Y. M. et al. Upregulation of CXCR4 is essential for HER2-mediated tumor metastasis. Cancer Cell 6, 459–469 (2004)

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FURTHER READING

  1. Epstein, R. The CXCL12–CXCR4 chemotactic pathway as a target of adjuvant breast cancer therapies. Nature Rev. Cancer 4, 901–909 (2004)

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Authors
  1. Nicola McCarthy
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McCarthy, N. One step closer. Nat Rev Cancer 5, 4 (2005). https://doi.org/10.1038/nrc1533

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  • DOI: https://doi.org/10.1038/nrc1533

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