Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells
Summary: 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 s...
| Main Authors: | , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-06-01
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| Series: | Cell Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124718308623 |
| _version_ | 1818364003907272704 |
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| author | Hirotaka Watanabe Kojiro Ishibashi Hiroki Mano Sho Kitamoto Nanami Sato Kazuya Hoshiba Mugihiko Kato Fumihiko Matsuzawa Yasuto Takeuchi Takanobu Shirai Susumu Ishikawa Yuka Morioka Toshiaki Imagawa Kazuyasu Sakaguchi Suguru Yonezawa Shunsuke Kon Yasuyuki Fujita |
| author_facet | Hirotaka Watanabe Kojiro Ishibashi Hiroki Mano Sho Kitamoto Nanami Sato Kazuya Hoshiba Mugihiko Kato Fumihiko Matsuzawa Yasuto Takeuchi Takanobu Shirai Susumu Ishikawa Yuka Morioka Toshiaki Imagawa Kazuyasu Sakaguchi Suguru Yonezawa Shunsuke Kon Yasuyuki Fujita |
| author_sort | Hirotaka Watanabe |
| collection | DOAJ |
| description | Summary: 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. : Watanabe et al. demonstrate that mutant p53 cells undergo necroptosis and are eliminated from epithelia via cell competition with surrounding normal cells. Moreover, the eradication of mutant p53 cells is suppressed within RasV12-transformed epithelia, suggesting that the order of oncogenic mutations in cancer development could be dictated by cell competition. Keywords: cell competition, p53, necroptosis, p53R273H, p53R175H, RasV12, multi-step cancer progression, MDCK cells, mouse intestinal organoids |
| first_indexed | 2024-12-13T21:57:28Z |
| format | Article |
| id | doaj.art-7b3d5f86dea4489d8d609ac4b73d0b9d |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T21:57:28Z |
| publishDate | 2018-06-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-7b3d5f86dea4489d8d609ac4b73d0b9d2022-12-21T23:30:06ZengElsevierCell Reports2211-12472018-06-01231337213729Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial CellsHirotaka Watanabe0Kojiro Ishibashi1Hiroki Mano2Sho Kitamoto3Nanami Sato4Kazuya Hoshiba5Mugihiko Kato6Fumihiko Matsuzawa7Yasuto Takeuchi8Takanobu Shirai9Susumu Ishikawa10Yuka Morioka11Toshiaki Imagawa12Kazuyasu Sakaguchi13Suguru Yonezawa14Shunsuke Kon15Yasuyuki Fujita16Division of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, JapanDivision of Disease Model Innovation, Institute for Genetic Medicine, Hokkaido University, Sapporo 060-0815, JapanGraduate 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, JapanGraduate 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, JapanDepartment of Human Pathology, Field of Oncology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima 890-8544, JapanDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan; Corresponding authorDivision of Molecular Oncology, Hokkaido University, Sapporo 060-0815, Japan; Graduate School of Chemical Sciences and Engineering, Hokkaido University, Sapporo 060-0815, Japan; Corresponding authorSummary: 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. : Watanabe et al. demonstrate that mutant p53 cells undergo necroptosis and are eliminated from epithelia via cell competition with surrounding normal cells. Moreover, the eradication of mutant p53 cells is suppressed within RasV12-transformed epithelia, suggesting that the order of oncogenic mutations in cancer development could be dictated by cell competition. Keywords: cell competition, p53, necroptosis, p53R273H, p53R175H, RasV12, multi-step cancer progression, MDCK cells, mouse intestinal organoidshttp://www.sciencedirect.com/science/article/pii/S2211124718308623 |
| spellingShingle | Hirotaka Watanabe Kojiro Ishibashi Hiroki Mano Sho Kitamoto Nanami Sato Kazuya Hoshiba Mugihiko Kato Fumihiko Matsuzawa Yasuto Takeuchi Takanobu Shirai Susumu Ishikawa Yuka Morioka Toshiaki Imagawa Kazuyasu Sakaguchi Suguru Yonezawa Shunsuke Kon Yasuyuki Fujita Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells Cell Reports |
| title | Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells |
| title_full | Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells |
| title_fullStr | Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells |
| title_full_unstemmed | Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells |
| title_short | Mutant p53-Expressing Cells Undergo Necroptosis via Cell Competition with the Neighboring Normal Epithelial Cells |
| title_sort | mutant p53 expressing cells undergo necroptosis via cell competition with the neighboring normal epithelial cells |
| url | http://www.sciencedirect.com/science/article/pii/S2211124718308623 |
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