最近一项用小鼠前列腺癌模型所做的实验研究，识别出了刺激转移形成的一个信号通道。当一个蛋白配体占据一个被称为RANK（receptor activator of nuclear factor κ B）的受体时，该通道被激发，并且它还依赖于这种激发和IKKα (IkB kinase a)的核转位。一旦进入细胞核中，被激发的IKKα就会抑制maspin基因转录，该转录的产物已被明确为前列腺癌和乳腺癌中细胞迁移和入侵的一个抑制成分。因此，RANK可能是前列腺癌或乳房肿瘤细胞中都有的转移行为的一个促进剂（启动子）。该研究成果被发表于4月5日出版的《自然》（Nature）杂志上。
部分英文原文：
Letter
Nature 446, 690-694 (5 April 2007) | doi:10.1038/nature05656; Received 5 December 2006; Accepted 2 February 2007; Published online 18 March 2007
Nuclear cytokine-activated IKK controls prostate cancer metastasis by repressing Maspin
Jun-Li Luo1, Wei Tan1, Jill M. Ricono2, Olexandr Korchynskyi1, Ming Zhang3, Steven L. Gonias2, David A. Cheresh2 & Michael Karin1
Laboratory of Gene Regulation and Signal Transduction, Department of Pharmacology and Cancer Center, School of Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, California 92093-0723, USA
Department of Pathology and the Moores Cancer Center, University of California, San Diego, La Jolla, California 92093-0803, USA
Baylor College of Medicine, Department of Molecular and Cellular Biology, One Baylor Plaza, Houston, Texas 77030, USA
Correspondence to: Michael Karin1 Correspondence and requests for materials should be addressed to M.K. (Email: karinoffice@ucsd.edu).
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Inflammation enhances tumour promotion through NF-B-dependent mechanisms1. NF-B was also proposed to promote metastatogenesis through epithelial–mesenchymal transition2. Yet a mechanistic link between inflammation and metastasis is missing. We identified a role for IB kinase (IKK), activated by receptor activator of NF-B (RANK/TNFRSF11A), in mammary epithelial proliferation during pregnancy3. Owing to similarities between mammary and prostate epithelia, we examined IKK involvement in prostate cancer and its progression. Here we show that a mutation that prevents IKK activation slows down CaP growth and inhibits metastatogenesis in TRAMP mice, which express SV40 T antigen in the prostate epithelium4. Decreased metastasis correlated with elevated expression of the metastasis suppressor Maspin5, the ablation of which restored metastatic activity. IKK activation by RANK ligand (RANKL/TNFSF11) inhibits Maspin expression in prostate epithelial cells, whereas repression of Maspin transcription requires nuclear translocation of active IKK. The amount of active nuclear IKK in mouse and human prostate cancer correlates with metastatic progression, reduced Maspin expression and infiltration of prostate tumours with RANKL-expressing inflammatory cells. We propose that tumour-infiltrating RANKL-expressing cells lead to nuclear IKK activation and inhibition of Maspin transcription, thereby promoting the metastatic phenotype.
