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March 22, 2014Molecular Oncology61 citationsOpen Access

14‐3‐3 and β‐catenin are secreted on extracellular vesicles to activate the oncogenic Wnt pathway

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SDShiri DovratMCMichal CaspiAZAlona Zilberberg

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Abstract

Aberrant activation of the canonical Wnt signal transduction pathway is involved in a large number of human diseases. β-catenin, the key effector protein of the canonical Wnt pathway, functions in the nucleus with T-cell factor/lymphoid enhancer factor (TCF/LEF) to activate expression of Wnt target genes. Here we show that members of the 14-3-3 protein family bind disheveled-2 (Dvl-2) and glycogen synthase-3β (GSK-3β) to attenuate the interaction between GSK-3β and β-catenin. Importantly, 14-3-3 and β-catenin form "bleb-like" structures and are secreted via extracellular vesicles to induce Wnt signaling activity in target cells. Our data suggest a novel way of transducing the oncogenic Wnt signal in which β-catenin is regulated by 14-3-3ζ through the formation of "oncosomes" that contain both the 14-3-3 and β-catenin proteins.

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Cite This Study

Dovrat et al. (2014) studied this question.

synapsesocial.com/papers/6a0891b6a8a781e4cde8a1c4https://doi.org/10.1016/j.molonc.2014.03.011
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