A link between inflammation and cancer has long been suspected but the exact molecular mechanisms connecting the two were not known. It is currently estimated that at least 20% of cancer mortality is associated with infection and inflammation. Thus understanding the underlying pathogenic mechanisms is of great importance. We have proposed that NF-κB transcription factors play a critical role in connecting inflammation to cancer and after 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 tumor promoting role for IKKβ and more recently identified a role for IKKα in the promotion of prostate cancer metastasis. Whereas the major tumor promoting function of IKKβ is dependent on NF-κB activation, the pro-metastatic function of IKKα is NF-κB 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 the 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.
This abstract was published in Cancer Immunity, a Cancer Research Institute journal that ceased publication in 2013 and is now provided online in association with Cancer Immunology Research.
- Copyright © 2007 by Michael Karin