中心体扩增导致染色体不稳定，在NSCLC发生发展中起重要作用。IKBKE属非经典IKB激酶，在中心体扩增中的作用及机制未见报道。课题组前期研究发现：①IKBKE在部分NSCLC高表达；②IKBKE转染H1299细胞，可定位于中心体并促进中心体扩增；③过表达IKBKE增强中心体数量调控分子PLK4蛋白表达，而MG132可抑制这种增强作用。基于上述现象提出：IKBKE是新的中心体蛋白，通过磷酸化修饰PLK4，增强其稳定性，抑制其泛素化降解，从而促进中心体扩增，导致NSCLC染色体不稳定。为证实该假说，本课题拟利用NSCLC细胞系及病理标本，从分子、细胞及组织水平，明确IKBKE的中心体定位特点和扩增作用，阐明IKBKE通过调控PLK4促进中心体扩增的分子机制，组织中进一步验证IKBKE与PLK4、中心体扩增的调控关系，评估其预后价值。研究结果将为NSCLC的防治提供新的理论基础和治疗靶点。

Centrosome amplification can result in chromosomal instability, which plays a crucial role in the development and progression of NSCLC. IKBKE is a member of non-canonical IKB kinase family, whose role in centrosome amplification remains unknown. Our previous work revealed that IKBKE overexpression was found in part of NSCLC, IKBKE could locate in centrosome and induce centrosome amplification after being transfected into H1299 cell line, and IKBKE could increase the expression of centrosome number modulator-PLK4 at protein level that could be inhibited by MG132 treatment. Base on above findings, we hypothesized that IKBKE be a new centrosome protein which induces centrosome amplification through phosphorylating PLK4, increasing its stability and inhibiting its ubiquitin degradation to promote the chromosomal instability of NSCLC. To test the hypothesis, we perform experiments at molecular, cellular and tissue levels with NSCLC cell lines and tissues to validate the role of IKBKE in centrosome localization and amplification, clarify the molecular mechanism of centrosome amplification induced by IKBKE through regulating PLK4, and verify the correlation of IKBKE with PLK4 and centrosome amplification and evaluate their prognostic value. Our results will provide novel theory basis and therapeutic targets for the treatment and prevention of NSCLC.