Emerging roles for the non-canonical IKKs in cancer.
The IκB Kinase (IKK)-related kinases TBK1 and IKKɛ have essential roles as regulators of innate immunity by modulating interferon and NF-κB signaling. Recent work has also implicated these non-canonical IKKs in malignant transformation. IKKɛ is amplified in ∼30% of breast cancers and transforms cells through the activation of NF-κB. 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 IKKɛ has begun to define their role(s) in promoting tumorigenesis. In this review, we will highlight the mechanisms by which IKKɛ and TBK1 orchestrate pathways involved in inflammation and cancer.
Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.
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D000230:Adenocarcinoma / Q000201:enzymology* / Q000276:immunology; D017209:Apoptosis / Q000276:immunology; D001943:Breast Neoplasms / Q000201:enzymology* / Q000276:immunology; D002289:Carcinoma, Non-Small-Cell Lung / Q000201:enzymology* / Q000276:immunology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D005260:Female; D006801:Humans; D051550:I-kappa B Kinase / Q000276:immunology / Q000378:metabolism*; D007113:Immunity, Innate; D007249:Inflammation / Q000201:enzymology / Q000276:immunology; D007372:Interferons / Q000276:immunology; D016328:NF-kappa B / Q000276:immunology / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000276:immunology / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000276:immunology / Q000378:metabolism; D016283:Proto-Oncogene Proteins p21(ras); D015398:Signal Transduction / Q000276:immunology; D018631:ras Proteins / Q000276:immunology / Q000378:metabolism
C117307:KRAS protein, human; D016328:NF-kappa B; D011518:Proto-Oncogene Proteins; D007372:Interferons; D017346:Protein Serine-Threonine Kinases; C403191:TBK1 protein, human; D051550:I-kappa B Kinase; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins