Emerging roles for the non-canonical IKKs in cancer

The I kappa B Kinase (IKK)-related kinases TBK1 and IKK epsilon have essential roles as regulators of innate immunity by modulating interferon and NF-kappa B signaling. Recent work has also implicated these non-canonical IKKs in malignant transformation. IKK epsilon is amplified in similar to 30% of breast cancers and transforms cells through the activation of NF-kappa B. TBK1 participates in RalB-mediated inflammatory responses and cell survival, and is essential for the survival of non-small cell lung cancers driven by oncogenic KRAS. The delineation of target substrates and downstream activities for TBK1 and IKK epsilon has begun to define their role(s) in promoting tumorigenesis. In this review, we will highlight the mechanisms by which IKKe and TBK1 orchestrate pathways involved in inflammation and cancer. Oncogene (2011) 30, 631-641; doi:10.1038/onc.2010.493; published online 1 November 2010