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Condensing and constraining WNT by TGF-β

Nature Cell Biology volume 23, pages 213–214 (2021)Cite this article

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TGF-β can antagonise or cooperate with WNT signalling, yet it is still unclear what mechanisms integrate the outcomes of these conserved pathways. A new study now reports that the formation of biomolecular condensates, dependent on the DACT1 protein, provides the spatial segregation needed for TGF-β to constrain WNT signalling.

The transforming growth factor beta (TGF-β) and canonical Wingless integration site (WNT)–β-catenin pathways are amongst the most well-studied cell signal transduction pathways in metazoan biology. The importance of the TGF-β and WNT pathways in development and human disease are well established. And yet, despite having at our disposal a vast catalogue of effector molecules that operate within these pathways, a fundamental question endures. How can the activation of these highly conserved cellular inputs result in such diverse biological outcomes? Indeed, depending on the context, TGF-β activation can either antagonise or cooperate with WNT–β-catenin1. In this issue of Nature Cell Biology, Esposito et al. shed new light on this long-standing paradox by uncovering a role for the TGF-β target gene Dishevelled Binding Antagonist of Beta Catenin 1(DACT1) in forming biomolecular condensates that constrain canonical WNT activation in cancer cells2.

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Fig. 1: Activation of canonical WNT and TGF-β receptors lead to distinct, but integrated downstream signalling pathways.

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Authors and Affiliations

  1. Department of Pathology, Yale University School of Medicine, New Haven, CT, USA

    Kiran D. Patel & Don X. Nguyen

  2. Yale Cancer Center, Yale University School of Medicine, New Haven, CT, USA

    Don X. Nguyen

  3. Department of Medicine (Medical Oncology), Yale University School of Medicine, New Haven, CT, USA

    Don X. Nguyen

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  1. Kiran D. Patel
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  2. Don X. Nguyen
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Correspondence to Don X. Nguyen.

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D.X.N. has received research support from AstraZeneca, Inc.

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Patel, K.D., Nguyen, D.X. Condensing and constraining WNT by TGF-β. Nat Cell Biol 23, 213–214 (2021). https://doi.org/10.1038/s41556-021-00649-2

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