An inhibitory role of NEK6 in TGFβ/Smad signaling pathway
نویسندگان
چکیده
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.
منابع مشابه
The Role of Wnt Signaling Pathway on the Expression of TGFβ 1 and TGFβ 2 in Cultured Rat Cortical Astrocytes
Introduction: Astrocytes, the most abundant glia in the central nervous system, modulate neuronal survival and function. Astrocytic functions are mediated by synthesis and secretion of wide ranges of polypeptides through mechanism (s) poorly understood. Among these, TGFβs are synthesized and released by the astrocytes. In this study, the involvement of Wnt signaling pathway on the synthesi...
متن کاملEffects of fibromodulin protein expression on NFkB and TGFβ signaling pathways in liver cancer cells
Introduction: The incidence rate of liver cancer is continuously increasing. Currently, gene therapy is applied to improve various medical issues such as cancer treatment approaches. Correspondingly, fibromodulin involves in many biological and physiological processes through interaction with growth factors and signaling pathway receptors. The aim of this study was to investigate the effects of...
متن کاملLAT-derived microRNAs in HSV-1 target SMAD3 and SMAD4 in TGF-β/Smad signaling pathway
Background: During its latent infection, HSV-1 produces only a miRNA precursor called LAT, which encodes six distinct miRNAs. Recent studies have suggested that some of these miRNAs could target cellular mRNAs. One of the key cell signaling pathways that can be affected by HSV-1 is the TGF-β/Smad pathway. Herein, we investigated the potential role of the LAT as well as three LAT-derived miRNAs ...
متن کاملIKK(α) controls canonical TGF(ß)-SMAD signaling to regulate genes expressing SNAIL and SLUG during EMT in panc1 cells.
The epithelial to mesenchymal transition (EMT) is a crucial step in tumor progression, and the TGFβ-SMAD signaling pathway is an inductor of EMT in many tumor types. One hallmark of EMT is downregulation of the adherens junction protein E-cadherin, a process mediated by transcription factors such as the zinc fingers SNAIL and SLUG. Here, we report that the catalytic IκB kinase (IKK) subunit IKK...
متن کاملERK1/2 pathway mediates epithelial-mesenchymal transition by cross-interacting with TGFβ/Smad and Jagged/Notch signaling pathways in lens epithelial cells.
Epithelial-mesenchymal transition (EMT) of lens epithelial cells (LECs) is the major pathological mechanism in anterior subcapsular cataract (ASC) and posterior capsule opacification (PCO), which are important causes of visual impairment. Extracellular signal-regulated kinase (ERK)1/2 pathway has been reported to play a major role in carcinogenesis, cancer metastasis and various fibrotic diseas...
متن کامل