title: Yes-associated protein 1 (YAP1) promotes human gallbladder tumor growth via activation of the AXL/MAPK pathway.
abstract: The transcriptional coactivator Yes-associated protein 1 (YAP1), a key regulator of cell proliferation and organ size in vertebrates, has been implicated in various malignancies. However, little is known about the expression and biological function of YAP1 in human gallbladder cancer (GBC). In this study we examined the clinical significance and biological functions of YAP1 in GBC and found that nuclear YAP1 and its target gene AXL were overexpressed in GBC tissues. We also observed a significant correlation between high YAP1 and AXL expression levels and worse prognosis. The depletion of YAP1 using lentivirus shRNAs significantly inhibited cell proliferation by inducing cell cycle arrest in S phase in concordance with the decrease of CDK2, CDC25A, and cyclin A, and resulted in increased cell apoptosis and invasive repression in GBC cell lines in vitro. Furthermore, knockdown of YAP1 also inhibited tumor growth in vivo. Additionally, we demonstrated that the activation of the AXL/MAPK pathway was involved in the oncogenic functions of YAP1 in GBC. These results demonstrated that YAP1 is a putative oncogene and represents a prognostic marker and potentially a novel therapeutic target for GBC.
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Maolan
authors.initials: M
authors.lastname: Li
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Lu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Fei
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Huaifeng
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of General Surgery, Shanxi Medical University Second Hospital, Taiyuan, China.
authors.forename: Bingtai
authors.initials: B
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiangsong
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Zhujun
authors.initials: Z
authors.lastname: Tan
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Zhang
authors.affiliation: Department of General Surgery, Shanxi Medical University Second Hospital, Taiyuan, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Gao
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jiasheng
authors.initials: J
authors.lastname: Mu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Shu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Runfa
authors.initials: R
authors.lastname: Bao
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Qichen
authors.initials: Q
authors.lastname: Ding
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Wenguang
authors.initials: W
authors.lastname: Wu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Gu
authors.affiliation: Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China; Institute of Biliary Tract Disease, Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: liuybphd@126.com.
authors.forename: Yingbin
authors.initials: Y
authors.lastname: Liu
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D017209:Apoptosis / Q000502:physiology; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism; D049109:Cell Proliferation / Q000502:physiology; D004789:Enzyme Activation; D005706:Gallbladder Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D064593:Heterografts; D006801:Humans; D020935:MAP Kinase Signaling System; D051379:Mice; D008819:Mice, Nude; D020928:Mitogen-Activated Protein Kinases / Q000235:genetics / Q000378:metabolism*; D009857:Oncogenes; D010750:Phosphoproteins / Q000096:biosynthesis / Q000235:genetics / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000502:physiology; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; D000094963:Axl Receptor Tyrosine Kinase
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C088374:YAP1 protein, human; D020794:Receptor Protein-Tyrosine Kinases; D020928:Mitogen-Activated Protein Kinases; D000094963:Axl Receptor Tyrosine Kinase
keywords: Cell cycle arrest; Cell proliferation; Gallbladder cancer; RNA interference; YAP1