Department of Medical Oncology, Dana Farber Cancer Institute, Boston, MA 02115, USA.
Oncogene. 2011 Feb 10;30(6):631-41. doi: 10.1038/onc.2010.493. Epub 2010 Nov 1.
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.
IKK 相关激酶 TBK1 和 IKKɛ 通过调节干扰素和 NF-κB 信号通路，在先天免疫中发挥着重要作用。最近的研究还表明这些非经典 IKK 在恶性转化中也有作用。IKKɛ 在约 30%的乳腺癌中扩增，并通过激活 NF-κB 来转化细胞。TBK1 参与 RalB 介导的炎症反应和细胞存活，并且对于由致癌 KRAS 驱动的非小细胞肺癌的存活是必需的。TBK1 和 IKKɛ 的靶底物和下游活性的描绘已经开始定义它们在促进肿瘤发生中的作用。在这篇综述中，我们将强调 IKKɛ 和 TBK1 协调参与炎症和癌症的途径的机制。
