An inhibitory role of NEK6 in TGFβ/Smad signaling pathway

The NEK6 (NIMA-related kinases 6) is reported to play po-tential 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 (TGF beta) pathway. Over-expression of NEK6 in hepatocellular carcinoma (HCC) cell lines suppresses TGF beta-mediated transcription activity in a kinase activity-dependent manner. In addition, NEK6 suppresses the cell growth arrest induced by TGF beta. Mechanically, NEK6 blocks nuclear translocation of Smad4, which is essential for TGF beta function. Moreover, we identified that NEK6 could be regulated by TGF beta and hypoxia. Our study sheds new light on the roles of NEK6 in canonical TGF beta/Smad pathway and tum-origenesis.