KLF2 inhibits TGF-β-mediated cancer cell motility in hepatocellular carcinoma  

作　　者：Yining Li Shuo Tu Yi Zeng Cheng Zhang Tian Deng Weicheng Luo Lingyan Lian Ling Chen Xiangyang Xiong Xiaohua Yan 

机构地区：[1]Departm ent of Biochem istry and Molecular Biology,School of Basic Medical Sciences,Nanchang University,Nanchang 330006,China [2]Institute of Biom edical Sciences,Nanchang University,Nanchang 330006,China [3]The Health Department of the First A ffiliated Hospital of Nanchang University,Nanchang 330006,China [4]The Second Affiliated Hospital of Nanchang University,Nanchang 330006,China

出　　处：《Acta Biochimica et Biophysica Sinica》2020年第5期485-494,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by the grants from the National Natural Science Foundation of China(Nos.31671460 and 31871378 to.X.Y),the Natural Science Foundation of Jiangxi Province of China(No.20171ACB21004 to XY and No.20192BAB205118 to S.T.),and the Special Funding Project for Graduate Student Innovation of Nanchang University(No.CX2019133 to YL.).

摘　　要：Feedback regulation plays a pivotal role in determining the intensity and duration of TGF-p signaling and subsequently affecting the pathophysiological roles of TGF-p,including those in liver malignancy.KLF2,a member of the Kruppel-like factor(KLF)fam ily transcription factors,has been implicated in impeding hepatocellular carcinoma(HCC)development.However,the underlying molecular mechanisms are not fully understood.In the present study,we found that TGF-p stimulates the expression of KLF2 gene in several HCC cell lines.KLF2 protein is able to inhibit TGF-p/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-p-induced target gene expression,therefore creating a novel negative feedback loop in TGFp signaling.Functionally,stably expression of KLF2 in HCCLM3 cells attenuated TGF-卜induced cancer cell motility in wound-healing and transwell assays by interfering with TGF-p-mediated upregulation of MMP2.Together,our results revealed that KLF2 protein has a tumor-suppressive function in HCC through a negative feedback loop over TGF-p signaling.

关 键 词：TGF-p signaling SMAD KLF2 feedback hepatocellular carcinoma cell motility 

分 类 号：R735.7[医药卫生—肿瘤]