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Tracking the Road from Inflammation to Cancer:
The Critical Role of IKK |
Michael Karin, PhD |
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University of California, San Diego
San Diego, California |
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A link between inflammation and cancer has long been suspected but the exact molecular mechanisms connecting the two were not known. After proposing that NF-κB transcription factors play a critical role in connecting inflammation to cancer and elucidating the role of the IκB kinase (IKK) complex in NF-κB activation we have set out to examine this hypothesis. Using mice bearing mutations in the genes coding for the IKKβ and IKKα catalytic subunits we found evidence for a critical role for IKKβ in tumor promotion and more recently identified a role for IKKα in stimulation of metastasis. Whereas the major tumorogenic function of IKKβ is mediated via NF-κB, the metastatic function of IKKα is NF-κβ independent. In addition to illustrating the critical role of the IKK catalytic subunits in linking inflammation and cancer, these results also identify new targets for development of novel types of anti-cancer therapies. Instead of targeting the cancer cell itself, such therapeutics should target processes that occur within inflammatory cells that are essential for cancer development and progression.
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