title: MEK1 promotes YAP and their interaction is critical for tumorigenesis in liver cancer.
abstract: Mitogen-activated protein kinase kinase 1 (MAP2K1/MEK1) as well as Yes-associated protein (YAP), the downstream effector of Hippo signaling pathway, is linked to hepatocarcinogenesis. However, little is known about whether and how MEK1 interacts with YAP. In this study, we find that MEK1-YAP interaction is critical for liver cancer cell proliferation and maintenance of transformed phenotypes both in vitro and in vivo. Moreover, MEK1 and YAP proteins are closely correlated in human liver cancer samples. Mechanistically, inhibition of MEK1 by both PD98059 and U0126 as well as RNAi reduces beta-transducin repeat containing E3 ubiquitin protein ligase (BTRC), which acts as a potential endogenous YAP protector.
authors.affiliation: Department of Clinical Laboratory Medicine, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China; Department of Laboratory Medicine, Chongqing Zhongshan Hospital, Chongqing 400013, China.
authors.forename: Lanlan
authors.initials: L
authors.lastname: Li
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wang
authors.forename: Yue
authors.initials: Y
authors.lastname: Zhang
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Lifang
authors.initials: L
authors.lastname: Ma
authors.forename: Wenhao
authors.initials: W
authors.lastname: Weng
authors.forename: Yongxia
authors.initials: Y
authors.lastname: Qiao
authors.forename: Weifan
authors.initials: W
authors.lastname: Xiao
authors.forename: Hongmei
authors.initials: H
authors.lastname: Wang
authors.forename: Wenjun
authors.initials: W
authors.lastname: Yu
authors.forename: Qiuhui
authors.initials: Q
authors.lastname: Pan
authors.forename: Yunyan
authors.initials: Y
authors.lastname: He
authors.forename: Fenyong
authors.initials: F
authors.lastname: Sun
mesh_terms: D000818:Animals; D063646:Carcinogenesis / Q000235:genetics / Q000378:metabolism*; D006528:Carcinoma, Hepatocellular / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D018797:Cell Cycle Proteins; D049109:Cell Proliferation; D057809:HEK293 Cells; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D048369:MAP Kinase Kinase 1 / Q000502:physiology*; D051379:Mice; D008819:Mice, Nude; D009687:Nuclear Proteins / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D014157:Transcription Factors / Q000378:metabolism*; D015533:Transcriptional Activation; D014407:Tumor Cells, Cultured; D015854:Up-Regulation
chemical_list: D018797:Cell Cycle Proteins; D009687:Nuclear Proteins; D014157:Transcription Factors; C456659:YY1AP1 protein, human; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; BTRC; Cell signaling; ERK1/2; HCC; Hippo pathway; IF; IHC; MTT; TMA; hepatocellular carcinoma; immunofluorescence; immunohistochemistry; tissue microarray analysis