A signalling pathway that enhances the formation of metastases in a mouse model of prostate cancer has been identified. The discovery, reported online in Nature, should aid our understanding of how cancer spreads.
Michael Karin and colleagues discovered that the pathway is activated by a protein that is likely to be expressed by tumour inflammatory cells. The protein is a ligand and when it binds to its receptor, called receptor activator of nuclear factor kappa-B (RANK), it triggers a chain reaction. A key kinase in the nuclear factor kappa-B signalling pathway is activated to function in the cell's nucleus and, this in turn, represses the transcription of a known metastasis suppressor called Maspin. The end result, in their mouse model at least, is that prostate cancer cells spread.
The results suggest that RANK may be a general promoter of metastasis. Importantly, its activating ligand is vastly upregulated in the late stages of prostate cancer, which may explain why metastasis is so common at that stage in the disease.
Michael Karin (University of California, La Jolla, CA, USA)
Abstract available online.
(C) Nature press release.
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