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Cooperative interaction between ERα and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis

Author

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  • Nastaran Mohammadi Ghahhari

    (Université de Genève, Sciences III)

  • Magdalena K. Sznurkowska

    (Institute of Molecular Health Sciences, ETH Zurich)

  • Nicolas Hulo

    (Université de Genève)

  • Lilia Bernasconi

    (Université de Genève, Sciences III)

  • Nicola Aceto

    (Institute of Molecular Health Sciences, ETH Zurich)

  • Didier Picard

    (Université de Genève, Sciences III)

Abstract

The epithelial to mesenchymal transition (EMT) has been proposed to contribute to the metastatic spread of breast cancer cells. EMT-promoting transcription factors determine a continuum of different EMT states. In contrast, estrogen receptor α (ERα) helps to maintain the epithelial phenotype of breast cancer cells and its expression is crucial for effective endocrine therapies. Determining whether and how EMT-associated transcription factors such as ZEB1 modulate ERα signaling during early stages of EMT could promote the discovery of therapeutic approaches to suppress metastasis. Here we show that, shortly after induction of EMT and while cells are still epithelial, ZEB1 modulates ERα-mediated transcription induced by estrogen or cAMP signaling in breast cancer cells. Based on these findings and our ex vivo and xenograft results, we suggest that the functional interaction between ZEB1 and ERα may alter the tissue tropism of metastatic breast cancer cells towards bone.

Suggested Citation

  • Nastaran Mohammadi Ghahhari & Magdalena K. Sznurkowska & Nicolas Hulo & Lilia Bernasconi & Nicola Aceto & Didier Picard, 2022. "Cooperative interaction between ERα and the EMT-inducer ZEB1 reprograms breast cancer cells for bone metastasis," Nature Communications, Nature, vol. 13(1), pages 1-19, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-29723-5
    DOI: 10.1038/s41467-022-29723-5
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    References listed on IDEAS

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