Nuclear cytokine-activated IKKα controls prostate cancer metastasis by repressing Maspin

Jun-Li Luo, Wei Tan, Jill M. Ricono, Olexandr Korchynskyi, Ming Zhang, Steven L. Gonias, David A. Cheresh and Michael Karin ()
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Jun-Li Luo: Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Wei Tan: Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Jill M. Ricono: University of California, San Diego, La Jolla, California 92093-0803, USA
Olexandr Korchynskyi: Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Ming Zhang: Baylor College of Medicine, One Baylor Plaza, Houston, Texas 77030, USA
Steven L. Gonias: University of California, San Diego, La Jolla, California 92093-0803, USA
David A. Cheresh: University of California, San Diego, La Jolla, California 92093-0803, USA
Michael Karin: Laboratory of Gene Regulation and Signal Transduction, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA

Nature, 2007, vol. 446, issue 7136, 690-694

Abstract: RANK key to metastasis Experiments in a mouse prostate cancer model have identified a signalling pathway that stimulates the formation of metastases. The pathway is initiated when a protein ligand occupies a receptor known as RANK (receptor activator of nuclear factor κB), and is dependent on the activation and nuclear translocation of IKKα (IκB kinase α). Once in the nucleus, activated IKKα represses maspin gene transcription, whose product is well established as an inhibitor of cell migration and invasion in prostate and breast cancer. RANK may therefore be a general promoter of metastatic behaviour in prostate or mammary carcinoma cells.

Date: 2007
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DOI: 10.1038/nature05656

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