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Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells.
Watanabe, Hirotaka; Ishibashi, Kojiro; Mano, Hiroki; Kitamoto, Sho; Sato, Nanami; Hoshiba, Kazuya; Kato, Mugihiko; Matsuzawa, Fumihiko; Takeuchi, Yasuto; Shirai, Takanobu; Ishikawa, Susumu; Morioka, Yuka; Imagawa, Toshiaki; Sakaguchi, Kazuyasu; Yonezawa, Suguru; Kon, Shunsuke; Fujita, Yasuyuki.
Afiliación
  • Watanabe H; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan.
  • Ishibashi K; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan.
  • Mano H; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan.
  • Kitamoto S; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan.
  • Sato N; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan.
  • Hoshiba K; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan.
  • Kato M; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan.
  • Matsuzawa F; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan.
  • Takeuchi Y; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan.
  • Shirai T; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan.
  • Ishikawa S; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan.
  • Morioka Y; Division of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, Japan.
  • Imagawa T; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan; Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
  • Sakaguchi K; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan; Laboratory of Biological Chemistry, Department of Chemistry, Faculty of Science, Hokkaido University, Sapporo 060-0810, Japan.
  • Yonezawa S; Department of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, Japan.
  • Kon S; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan. Electronic address: kon44@igm.hokudai.ac.jp.
  • Fujita Y; Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan. Electronic address: yasu@igm.hokudai.ac.jp.
Cell Rep ; 23(13): 3721-3729, 2018 06 26.
Article en En | MEDLINE | ID: mdl-29949757
p53 is a tumor suppressor protein, and its missense mutations are frequently found in human cancers. During the multi-step progression of cancer, p53 mutations generally accumulate at the mid or late stage, but not in the early stage, and the underlying mechanism is still unclear. In this study, using mammalian cell culture and mouse ex vivo systems, we demonstrate that when p53R273H- or p53R175H-expressing cells are surrounded by normal epithelial cells, mutant p53 cells undergo necroptosis and are basally extruded from the epithelial monolayer. When mutant p53 cells alone are present, cell death does not occur, indicating that necroptosis results from cell competition with the surrounding normal cells. Furthermore, when p53R273H mutation occurs within RasV12-transformed epithelia, cell death is strongly suppressed and most of the p53R273H-expressing cells remain intact. These results suggest that the order of oncogenic mutations in cancer development could be dictated by cell competition.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor Límite: Animals Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Japón

Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Proteína p53 Supresora de Tumor Límite: Animals Idioma: En Revista: Cell Rep Año: 2018 Tipo del documento: Article País de afiliación: Japón