title: Cell competition in mouse NIH3T3 embryonic fibroblasts is controlled by the activity of Tead family proteins and Myc.
abstract: Cell competition is a short-range communication originally observed in Drosophila. Relatively little is known about cell competition in mammals or in non-epithelial cells. Hippo signaling and its downstream transcription factors of the Tead family, control cell proliferation and apoptosis. Here, we established an in vitro model system that shows cell competition in mouse NIH3T3 embryo fibroblast cells. Co-culture of Tead-activity-manipulated cells with normal (wild-type) cells caused cell competition. Cells with reduced Tead activity became losers, whereas cells with increased Tead activity became super-competitors. Tead directly regulated Myc RNA expression, and cells with increased Myc expression also became super-competitors. At low cell density, cell proliferation required both Tead activity and Myc. At high cell density, however, reduction of either Tead activity or Myc was compensated for by an increase in the other, and this increase was sufficient to confer 'winner' activity. Collectively, NIH3T3 cells have cell competition mechanisms similar to those regulated by Yki and Myc in Drosophila. Establishment of this in vitro model system should be useful for analyses of the mechanisms of cell competition in mammals and in fibroblasts.
authors.affiliation: Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Mamada
authors.affiliation: Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Sato
authors.affiliation: Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan.
authors.forename: Mitsunori
authors.initials: M
authors.lastname: Ota
authors.affiliation: Department of Cell Fate Control, Institute of Molecular Embryology and Genetics, Kumamoto University, Kumamoto, Kumamoto 860-0811, Japan sasaki@kumamoto-u.ac.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Sasaki
mesh_terms: D016475:3T3 Cells; D048868:Adaptor Proteins, Signal Transducing / Q000037:antagonists & inhibitors / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D053148:Caspase 3 / Q000378:metabolism; D002450:Cell Communication / Q000235:genetics / Q000502:physiology*; D018797:Cell Cycle Proteins; D002460:Cell Line; D049109:Cell Proliferation / Q000235:genetics; D055515:Cysteine-Rich Protein 61 / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D004330:Drosophila / Q000378:metabolism; D029721:Drosophila Proteins / Q000378:metabolism; D004789:Enzyme Activation / Q000235:genetics; D005347:Fibroblasts; D000090683:Hippo Signaling Pathway; D051379:Mice; D009687:Nuclear Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000037:antagonists & inhibitors / Q000378:metabolism; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering; D015398:Signal Transduction / Q000235:genetics; D000091262:TEA Domain Transcription Factors; D015534:Trans-Activators / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D000091102:YAP-Signaling Proteins
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C491850:CCN1 protein, mouse; D018797:Cell Cycle Proteins; D055515:Cysteine-Rich Protein 61; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C489428:Myc protein, mouse; D009687:Nuclear Proteins; D010750:Phosphoproteins; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000091262:TEA Domain Transcription Factors; C083215:Tead1 protein, mouse; C486310:Tead2 protein, mouse; D015534:Trans-Activators; D014157:Transcription Factors; D000091102:YAP-Signaling Proteins; C486223:Yap1 protein, mouse; C503814:Yki protein, Drosophila; D017346:Protein Serine-Threonine Kinases; D053148:Caspase 3
keywords: Cell competition; Myc; NIH3T3 cells; Tead