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

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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.

Original languageEnglish
Article number171
JournalMolecular Cancer
Volume17
Issue number1
Pages (from-to)1-6
Number of pages6
ISSN1476-4598
DOIs
Publication statusPublished - 2018

    Research areas

  • Breast cancer, shRNA screening, Collective migration, Non-EMT

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