title: RUNX3 is a novel negative regulator of oncogenic TEAD-YAP complex in gastric cancer.
abstract: Runt-related transcription factor 3 (RUNX3) is a well-documented tumour suppressor that is frequently inactivated in gastric cancer. Here, we define a novel mechanism by which RUNX3 exerts its tumour suppressor activity involving the TEAD-YAP complex, a potent positive regulator of proliferative genes. We report that the TEAD-YAP complex is not only frequently hyperactivated in liver and breast cancer, but also confers a strong oncogenic activity in gastric epithelial cells. The increased expression of TEAD-YAP in tumour tissues significantly correlates with poorer overall survival of gastric cancer patients. Strikingly, RUNX3 physically interacts with the N-terminal region of TEAD through its Runt domain. This interaction markedly reduces the DNA-binding ability of TEAD that attenuates the downstream signalling of TEAD-YAP complex. Mutation of RUNX3 at Arginine 122 to Cysteine, which was previously identified in gastric cancer, impairs the interaction between RUNX3 and TEAD. Our data reveal that RUNX3 acts as a tumour suppressor by negatively regulating the TEAD-YAP oncogenic complex in gastric carcinogenesis.
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Y
authors.initials: Y
authors.lastname: Qiao
authors.affiliation: Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore.
authors.forename: S J
authors.initials: SJ
authors.lastname: Lin
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Y
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: D C-C
authors.initials: DC
authors.lastname: Voon
authors.affiliation: Department of Haematology and Oncology, National University Cancer Institute, National University Health System, Singapore.
authors.forename: F
authors.initials: F
authors.lastname: Zhu
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: L S H
authors.initials: LS
authors.lastname: Chuang
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: T
authors.initials: T
authors.lastname: Wang
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Cancer Therapeutics and Stratified Oncology, Genome Institute of Singapore, Singapore.|Cancer and Stem Cell Biology Program, Duke-NUS Graduate Medical School, Singapore.|Cellular and Molecular Research, National Cancer Centre, Singapore.
authors.forename: P
authors.initials: P
authors.lastname: Tan
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.|Department of Haematology and Oncology, National University Cancer Institute, National University Health System, Singapore.
authors.forename: S C
authors.initials: SC
authors.lastname: Lee
authors.affiliation: NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
authors.forename: K G
authors.initials: KG
authors.lastname: Yeoh
authors.affiliation: NUS Yong Loo Lin School of Medicine, National University of Singapore, Singapore.|Mechanobiology Institute (MBI), Singapore.|Institute of Molecular and Cell Biology (IMCB), A*STAR, Singapore.
authors.forename: M
authors.initials: M
authors.lastname: Sudol
authors.affiliation: Cancer Science Institute of Singapore, National University of Singapore, Singapore.
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
mesh_terms: D000595:Amino Acid Sequence; D063646:Carcinogenesis; D045744:Cell Line, Tumor; D050677:Core Binding Factor Alpha 3 Subunit / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D004247:DNA / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism; D006801:Humans; D009154:Mutation; D000072756:Protein Conformation, alpha-Helical; D000072417:Protein Domains; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism*
chemical_list: D050677:Core Binding Factor Alpha 3 Subunit; D014157:Transcription Factors; D004247:DNA