title: Mutual interaction between YAP and c-Myc is critical for carcinogenesis in liver cancer.
abstract: Yes-associated protein (YAP), the downstream effector of Hippo signaling pathway as well as c-Myc has been linked to hepatocarcinogenesis. However, little is known about whether and how YAP and c-Myc interacts with each other. In this study, we find YAP-c-Myc interaction is critical for liver cancer cell both in vitro and in vivo. Moreover, both c-Myc and YAP proteins are closely correlated in human liver cancer samples. Mechanistically, YAP promotes c-Myc transcriptional output through c-Abl. By contrast, c-Myc enhances protein expression independent of transcription. Taken together, our study uncovers a novel positive auto-regulatory feedback loop underlying the interaction between YAP and c-Myc in liver cancer, suggesting YAP and c-Myc links Hippo/YAP and c-Myc pathways, and thus may be helpful in the development of effective diagnosis and treatment strategies against liver cancer.
authors.affiliation: Department of Central Laboratory, Shanghai Tenth People's Hospital of Tongji University, Shanghai 200072, China.
authors.forename: Weifan
authors.initials: W
authors.lastname: Xiao
authors.forename: Jiayi
authors.initials: J
authors.lastname: Wang
authors.forename: Chao
authors.initials: C
authors.lastname: Ou
authors.forename: Yue
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: Qiuhui
authors.initials: Q
authors.lastname: Pan
authors.forename: Fenyong
authors.initials: F
authors.lastname: Sun
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000378:metabolism*; D000818:Animals; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D006801:Humans; D008099:Liver / Q000378:metabolism / Q000473:pathology*; D008113:Liver Neoplasms / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D010750:Phosphoproteins / Q000378:metabolism*; D060066:Protein Interaction Maps; D016315:Proto-Oncogene Proteins c-abl / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000378:metabolism*; D015398:Signal Transduction; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D018797:Cell Cycle Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; C486223:Yap1 protein, mouse; D016315:Proto-Oncogene Proteins c-abl
keywords: 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide; Gene regulation; HCC; Hepatocellular carcinoma; Hippo pathway; IF; IHC; MTT; Promoter; Protein stability; TMA; hepatocellular carcinoma; immunofluorescence; immunohistochemistry; tissue microarray