Article open access publication

Aggressiveness of non-EMT breast cancer cells relies on FBXO11 activity

Molecular Cancer, Springer Nature, ISSN 1476-4598

Volume 17, 1, 2018

DOI:10.1186/s12943-018-0918-6, Dimensions: pub.1110518190, PMC: PMC6287350, PMID: 30526604,

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Organisations

  1. (1) University of Copenhagen, grid.5254.6, KU
  2. (2) Oslo University Hospital, grid.55325.34

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Denmark

Norway

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Europe

Description

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.

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University of Copenhagen

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Times Cited: 5

Field Citation Ratio (FCR): 2.28

Relative Citation ratio (RCR): 0.33

Open Access Info

Pure Gold