An inhibitory role of NEK6 in TGFß/Smad signaling pathway

Abstract

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