MEK1 promotes YAP and their interaction is critical for tumorigenesis in liver cancer |
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| Authors: | Lanlan Li Jiayi Wang Yue Zhang Yan Zhang Lifang Ma Wenhao Weng Yongxia Qiao Weifan Xiao Hongmei Wang Wenjun Yu Qiuhui Pan Yunyan He Fenyong Sun |
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| Affiliation: | 1. Department of Clinical Laboratory Medicine, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072, China;2. Department of Laboratory Medicine, Chongqing Zhongshan Hospital, Chongqing 400013, China;3. Department of Central Laboratory, Shanghai Tenth People’s Hospital of Tongji University, Shanghai 200072, China;4. School of Public Health, Shanghai Jiaotong University, Shanghai 200025, China |
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| 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. |
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| Keywords: | HCC, hepatocellular carcinoma IF, immunofluorescence IHC, immunohistochemistry TMA, tissue microarray analysis MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide |
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