Zuo Jie, Ma Haijie, Cai Hao, Wu Yanhua, Jiang Wei, Yu Long
State Key Laboratory of Genetic Engineering, Institute of Genetics, Fudan University, Shanghai 200433, PR China.
Cell and Molecular Biology Laboratory, Zhoushan Hospital, Zhejiang, China.
BMB Rep. 2015 Aug;48(8):473-8. doi: 10.5483/bmbrep.2015.48.8.225.
The NEK6 (NIMA-related kinases 6) is reported to play potential roles in tumorigenesis. Although it is suggested to function in several cellular pathways, the underlying mechanism in tumorigenesis is still largely unknown. In the present study, we discovered interaction of NEK6 with Smad4, a key member of transforming growth factor beta (TGFβ) pathway. Over-expression of NEK6 in hepatocellular carcinoma (HCC) cell lines suppresses TGFβ-mediated transcription activity in a kinase activity-dependent manner. In addition, NEK6 suppresses the cell growth arrest induced by TGFβ. Mechanically, NEK6 blocks nuclear translocation of Smad4, which is essential for TGFβ function. Moreover, we identified that NEK6 could be regulated by TGFβ and hypoxia. Our study sheds new light on the roles of NEK6 in canonical TGFβ/Smad pathway and tumorigenesis.
据报道，NEK6（NIMA相关激酶6）在肿瘤发生中发挥潜在作用。尽管有人认为它在多种细胞途径中起作用，但肿瘤发生的潜在机制仍 largely未知。在本研究中，我们发现NEK6与Smad4相互作用，Smad4是转化生长因子β（TGFβ）途径的关键成员。在肝癌（HCC）细胞系中过表达NEK6以激酶活性依赖的方式抑制TGFβ介导的转录活性。此外，NEK6抑制TGFβ诱导的细胞生长停滞。从机制上讲，NEK6阻止Smad4的核转位，而Smad4的核转位是TGFβ功能所必需的。此外，我们发现NEK6可受TGFβ和缺氧调节。我们的研究为NEK6在经典TGFβ/Smad途径和肿瘤发生中的作用提供了新的线索。
