The IkB kinase - a bridge between inflammation
and cancer
Michael Karin
【期刊名称】《细胞研究（英文版）》 【年(卷),期】2008(018)003
【摘要】Apotential link between inflammation and cancer has been suspected for over a century, but the exact molecular mechanisms connecting the two remained nebulous. We proposed that NF-kB transcription factors regulated via the IkB kinase (IKK) complex play a critical role in coupling inflammation and cancer and have set out to test this hypothesis in mouse models of cancer. Using mice bearing mutations in the genes coding for the IKK(i and IKKa catalytic subunits we obtained evidence supporting a critical role for IKKp in tumor promotion and more recently identified the involvement of IKKa in metastatogenesis. Whereas the major pro-tumorigenic function of IKKp is mediated via NF-kB, the pro-metastatic function of IKKa is NF-KB-independent. In addition to illustrating the critical roles of the two IKK molecules in linking inflammation and cancer and providing an explanation for increased cancer risk in response to persistent infections and inflammation, these results also identify new targets for development of novel anti-cancer therapies and preventive strategies. Instead of targeting the cancer cell itself, as done by conventional anti-
The IkB kinase - a bridge between inflammation and cancer
