【摘 要】
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Feedback regulation plays a pivotal role in determining the intensity and duration of TGF-β signaling and subsequently affecting the pathophysiological roles o
【机 构】
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Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Nanchang Univers
论文部分内容阅读
Feedback regulation plays a pivotal role in determining the intensity and duration of TGF-β signaling and subsequently affecting the pathophysiological roles of TGF-β,including those in iver malignancy.KLF2,a member of the Krüppel-like factor (KLF) family transcription factors,has been implicated in mpeding hepatocellular carcinoma (HCC) development.However,the underlying molecular mechanisms are not fully understood.In the present study,we found that TGF-β stimulates the expression of KLF2 gene in several HCC cell lines.KLF2 protein is able to inhibit TGF-β/Smad signaling in HCC cells as assessed by luciferase reporter assay.Further studies indicated that KLF2 inhibits the transcriptional activity of Smad2/3 and Smad4 and ameliorates TGF-β-induced target gene expression,therefore creating a novel negative feedback loop in TGF-β signaling.Functionally,stably expression of KLF2 in HCCLM3 cells attenuated TGF-β-induced cancer cell motility in wound-healing and transwell assays by interfering with TGF-(β-mediated upregulation of MMP2.Together,our results revealed that KLF2 protein has a tumor-suppress ve function in HCC through a negative feedback loop over TGF-β signaling.
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