title: FOXM1 regulated by ERK pathway mediates TGF-β1-induced EMT in NSCLC.
abstract: FOXM1, a member of the Forkhead transcriptional family, plays an important role in the EMT process, and transforming growth factor-β1 (TGF-β1) has been identified as the most potent factor that can independently induce EMT in various types of cancer cells. Here we examine the important role of FOXM1 in TGF-β1-induced EMT and investigate the mechanism underlying the relationship between TGF-β1 and FOXM1. Lentivirus-mediated transfection was used to stably upregulate the expression of FOXM1, and a small interfering RNA (siRNA) was introduced to silence the expression of FOXM1. Transwell and wound-healing assays were then performed to assess the invasion and motility potential of non-small cell lung cancer (NSCLC) cells. The NSCLC cell lines exhibited EMT characteristics, including an elongated fibroblastoid shape, induced expression of EMT marker proteins, and increased migratory and invasive potential after induction with TGF-β1. The overexpression of FOXM1 enhanced TGF-β1-induced EMT in NSCLC cells. Knockdown of FOXM1 reversed TGF-β1-induced EMT in NSCLC cell lines but had no effect on the phosphorylation level of ERK. Additionally, U0126, an ERK signaling inhibitor, exerted a reversible effect on TGF-β1-induced EMT and inhibited FOXM1 expression. FOXM1 regulated by the ERK pathway can mediate TGF-β1-induced EMT in NSCLC and is a potential target for the treatment of NSCLC.
authors.affiliation: Department of Oncology, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: Fei-Fei
authors.initials: FF
authors.lastname: Kong
authors.affiliation: Department of General Surgery, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: You-Long
authors.initials: YL
authors.lastname: Zhu
authors.affiliation: Department of Oncology, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: Hai-Hua
authors.initials: HH
authors.lastname: Yuan
authors.affiliation: Department of Oncology, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: Jiong-Yi
authors.initials: JY
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: Mei
authors.initials: M
authors.lastname: Zhao
authors.affiliation: Department of Oncology, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: Xiao-Di
authors.initials: XD
authors.lastname: Gong
authors.affiliation: Department of Oncology, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: Feng
authors.initials: F
authors.lastname: Liu
authors.affiliation: Department of Oncology, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: Wen-Ying
authors.initials: WY
authors.lastname: Zhang
authors.affiliation: Metabolic Disease Bio-Bank, Shanghai Jiao Tong University Affiliated Sixth Peoples Hospital, Shanghai Diabetes Institute,Shanghai Key Laboratory of Diabetes MellitusShanghaiChina.
authors.forename: Cong-Rong
authors.initials: CR
authors.lastname: Wang
authors.affiliation: Department of Oncology, Shanghai 3rd Peoples Hospital, School of Medicine, Shanghai Jiao Tong UniversityShanghaiChina.
authors.forename: Bin
authors.initials: B
authors.lastname: Jiang
mesh_terms: D014408:Biomarkers, Tumor / Q000378:metabolism; D002070:Butadienes / Q000494:pharmacology; D002289:Carcinoma, Non-Small-Cell Lung / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects / Q000235:genetics; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000473:pathology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D058990:Molecular Targeted Therapy; D009361:Neoplasm Invasiveness / Q000235:genetics; D009570:Nitriles / Q000494:pharmacology; D034741:RNA, Small Interfering / Q000235:genetics; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D019076:Transgenes / Q000235:genetics; D014945:Wound Healing / Q000235:genetics
chemical_list: D014408:Biomarkers, Tumor; D002070:Butadienes; C107585:FOXM1 protein, human; D000072278:Forkhead Box Protein M1; D051858:Forkhead Transcription Factors; D009570:Nitriles; D034741:RNA, Small Interfering; D053773:Transforming Growth Factor beta1; C113580:U 0126