Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity
Abstract Tumorigenesis is increasingly considered to rely on subclones of cells poised to undergo an epithelial to mesenchymal transition (EMT) program. We and others have provided evidence, however, that the tumorigenesis of human breast cancer is not always restricted to typical EMT cells but is a...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2018-12-01
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| Series: | Molecular Cancer |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12943-018-0918-6 |
| _version_ | 1819211166611668992 |
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| author | Sofie Otzen Bagger Branden Michael Hopkinson Deo Prakash Pandey Mads Bak Andreas Vincent Brydholm Rene Villadsen Kristian Helin Lone Rønnov-Jessen Ole William Petersen Jiyoung Kim |
| author_facet | Sofie Otzen Bagger Branden Michael Hopkinson Deo Prakash Pandey Mads Bak Andreas Vincent Brydholm Rene Villadsen Kristian Helin Lone Rønnov-Jessen Ole William Petersen Jiyoung Kim |
| author_sort | Sofie Otzen Bagger |
| collection | DOAJ |
| description | Abstract Tumorigenesis is increasingly considered to rely on subclones of cells poised to undergo an epithelial to mesenchymal transition (EMT) program. We and others have provided evidence, however, that the tumorigenesis of human breast cancer is not always restricted to typical EMT cells but is also somewhat paradoxically conveyed by subclones of apparently differentiated, non-EMT cells. Here we characterize such non-EMT-like and EMT-like subclones. Through a loss-of-function screen we found that a member of the E3 ubiquitin ligase complexes, FBXO11, specifically fuels tumor formation of a non-EMT-like clone by restraining the p53/p21 pathway. Interestingly, in the related EMT-like clone, FBXO11 operates through the BCL2 pathway with little or no impact on tumorigenesis. These data command caution in attempts to assess tumorigenesis prospectively based on EMT profiling, and they emphasize the importance of next generation subtyping of tumors, that is at the level of clonal composition. |
| first_indexed | 2024-12-23T06:22:45Z |
| format | Article |
| id | doaj.art-bb303bc87ac34978b5b00ebf17386278 |
| institution | Directory Open Access Journal |
| issn | 1476-4598 |
| language | English |
| last_indexed | 2024-12-23T06:22:45Z |
| publishDate | 2018-12-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Cancer |
| spelling | doaj.art-bb303bc87ac34978b5b00ebf173862782022-12-21T17:57:09ZengBMCMolecular Cancer1476-45982018-12-011711610.1186/s12943-018-0918-6Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activitySofie Otzen Bagger0Branden Michael Hopkinson1Deo Prakash Pandey2Mads Bak3Andreas Vincent Brydholm4Rene Villadsen5Kristian Helin6Lone Rønnov-Jessen7Ole William Petersen8Jiyoung Kim9Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenDepartment of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenBiotech Research and Innovation Centre (BRIC), University of CopenhagenDepartment of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenDepartment of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenDepartment of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenNovo Nordisk Foundation Center for Stem Cell Biology (DanStem), University of CopenhagenSection for Cell Biology and Physiology, Department of Biology, Faculty of Science, University of Copenhagen, Universitetsparken 13Department of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenDepartment of Cellular and Molecular Medicine, Faculty of Health Sciences, University of CopenhagenAbstract Tumorigenesis is increasingly considered to rely on subclones of cells poised to undergo an epithelial to mesenchymal transition (EMT) program. We and others have provided evidence, however, that the tumorigenesis of human breast cancer is not always restricted to typical EMT cells but is also somewhat paradoxically conveyed by subclones of apparently differentiated, non-EMT cells. Here we characterize such non-EMT-like and EMT-like subclones. Through a loss-of-function screen we found that a member of the E3 ubiquitin ligase complexes, FBXO11, specifically fuels tumor formation of a non-EMT-like clone by restraining the p53/p21 pathway. Interestingly, in the related EMT-like clone, FBXO11 operates through the BCL2 pathway with little or no impact on tumorigenesis. These data command caution in attempts to assess tumorigenesis prospectively based on EMT profiling, and they emphasize the importance of next generation subtyping of tumors, that is at the level of clonal composition.http://link.springer.com/article/10.1186/s12943-018-0918-6Breast cancershRNA screeningCollective migrationNon-EMT |
| spellingShingle | Sofie Otzen Bagger Branden Michael Hopkinson Deo Prakash Pandey Mads Bak Andreas Vincent Brydholm Rene Villadsen Kristian Helin Lone Rønnov-Jessen Ole William Petersen Jiyoung Kim Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity Molecular Cancer Breast cancer shRNA screening Collective migration Non-EMT |
| title | Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity |
| title_full | Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity |
| title_fullStr | Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity |
| title_full_unstemmed | Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity |
| title_short | Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity |
| title_sort | aggressiveness of non emt breast cancer cells relies on fbxo11 activity |
| topic | Breast cancer shRNA screening Collective migration Non-EMT |
| url | http://link.springer.com/article/10.1186/s12943-018-0918-6 |
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