Flotillin1 promotes EMT of human small cell lung cancer via TGF-β signaling pathway

查看全文 作　　者：Lianmei [1,2]Zhao;Jie [2]Li;Yueping [3]Liu;Wei [1]Zhou;Yanan [2]Shan;Xinyi [1]Fan;Xinliang [2]Zhou;Baoen [2]Shan;Yongmei [1]Song;Qimin [1,4]Zhan

机构地区：[1]State Key Laboratory of Molecular Oncology, National Cancer Center/Cancer Hospital, Chinese Academy of Medical Sciences&Peking Union Medical College;[2]Research Center, The Fourth Hospital of Hebei Medical University;[3]Pathology Department, The Fourth Hospital of Hebei Medical University;[4]Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education/Beijing), Laboratory of Molecular Oncology, Peking University Cancer Hospital &Institute

出　　处：《Cancer Biology & Medicine》索引2018年第15卷第4期,共15页

基　　金：the National Natural Science Foundation of China (Grant No. 81472661, 81490753, 81230047, 81672743, 81772550); Postdoctoral Science Foundation Program of Chinese Academy of Medical Science & Peking Medical College 摘　　要：Objective:Small cell lung carcinoma(SCLC)is considered one of the most aggressive types of lung cancer due to its rapid growth and early metastasis.No tumor markers or therapeutic targets have been demonstrated to be specific or effective in SCLC to date.This study aims to evaluate the potential of Flotillin1(Flot1)as a target of SCLC treatment.Methods:Flot1 expression level in the tissue of SCLC and other tissue of lung disease was detected using immunohistochemical staining.Transwell and Matrigel assays were employed to examine migration and invasion of cancer cells.Flow cytometry and xCELLigence system were used to evaluate cell apoptosis and cell viability,respectively.Expression levels of Flot1,epithelialmesenchymal transition(EMT)marker E-cadherin,vimentin,cyclinD1,TGF-β-Smad2/3,and p-AKT were examined using Western blot.Furthermore,xenograft tumor in nude mice was used to evaluate the growth and metastasis of NCI-H446 cells in vivo.Results:Our results demonstrated that Flot1 is highly expressed in SCLC samples and that its expression correlates strongly with clinical stage,distant metastasis,and poor survival.The knockdown of Flot1 decreased the growth,migration,and invasiveness of SCLC cells and reversed EMT phenotype in vitro and in vivo,while enhanced Flot1 expression exhibited the opposite behavior.Gene expression profile analysis demonstrated that Flot1-regulated genes frequently mapped to the AKT and TGF-β-Smad2/3pathways.Our results further revealed that Flot1 affected the progression of SCLC via regulation of EMT progression.Conclusions:These findings indicated an oncogenic role of Flot1 via promoting EMT in SCLC and suggested its potential as a tumor marker and prognostic indicator. 关键词：Flotillin1 small cell LUNG cancer EMT TGF-β-smad2/3

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Flotillin1 promotes EMT of human small cell lung cancer via TGF-β signaling pathway

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