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ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types

Author

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  • Waltraut Lehmann

    (University of Freiburg Medical Center
    Faculty of Biology, Albert-Ludwigs-University Freiburg)

  • Dirk Mossmann

    (Faculty of Biology, Albert-Ludwigs-University Freiburg
    Institute for Biochemistry and Molecular Biology, ZMBZ, Albert-Ludwigs-University Freiburg)

  • Julia Kleemann

    (Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg)

  • Kerstin Mock

    (University of Freiburg Medical Center
    Faculty of Biology, Albert-Ludwigs-University Freiburg)

  • Chris Meisinger

    (Institute for Biochemistry and Molecular Biology, ZMBZ, Albert-Ludwigs-University Freiburg
    BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg)

  • Tilman Brummer

    (BIOSS Centre for Biological Signalling Studies, Albert-Ludwigs-University Freiburg
    Institute for Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg)

  • Ricarda Herr

    (Institute for Molecular Medicine and Cell Research, Albert-Ludwigs-University Freiburg)

  • Simone Brabletz

    (Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg)

  • Marc P. Stemmler

    (Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg)

  • Thomas Brabletz

    (Nikolaus-Fiebiger-Center for Molecular Medicine, FAU University Erlangen-Nürnberg)

Abstract

Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a ‘common ZEB1/YAP target gene set’, thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings.

Suggested Citation

  • Waltraut Lehmann & Dirk Mossmann & Julia Kleemann & Kerstin Mock & Chris Meisinger & Tilman Brummer & Ricarda Herr & Simone Brabletz & Marc P. Stemmler & Thomas Brabletz, 2016. "ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types," Nature Communications, Nature, vol. 7(1), pages 1-15, April.
    • Handle: RePEc:nat:natcom:v:7:y:2016:i:1:d:10.1038_ncomms10498
    DOI: 10.1038/ncomms10498
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    Cited by:

    1. 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.
    2. Anat Kreimer & Tal Ashuach & Fumitaka Inoue & Alex Khodaverdian & Chengyu Deng & Nir Yosef & Nadav Ahituv, 2022. "Massively parallel reporter perturbation assays uncover temporal regulatory architecture during neural differentiation," Nature Communications, Nature, vol. 13(1), pages 1-15, December.

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