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

Shiri Dovrat, Michal Caspi, Alona Zilberberg, Lital Lahav, Anastasia Firsow, Hila Gur, Rina Rosin-Arbesfeld

Research output: Contribution to journalArticlepeer-review

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.

Original languageEnglish
Pages (from-to)894-911
Number of pages18
JournalMolecular Oncology
Volume8
Issue number5
DOIs
StatePublished - Jul 2014

Keywords

  • 14-3-3
  • Exosomes
  • Extracellular vesicles
  • Wnt signaling
  • β-catenin

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