Open Access14‐3‐3 and β‐catenin are secreted on extracellular vesicles to activate the oncogenic Wnt pathway
Author(s) -
Dovrat Shiri,
Caspi Michal,
Zilberberg Alona,
Lahav Lital,
Firsow Anastasia,
Gur Hila,
Rosin-Arbesfeld Rina
Publication year - 2014
Publication title -
molecular oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.332
H-Index - 88
eISSN - 1878-0261
pISSN - 1574-7891
DOI - 10.1016/j.molonc.2014.03.011
Subject(s) - wnt signaling pathway , lrp6 , lrp5 , microbiology and biotechnology , signal transduction , catenin , beta catenin , biology , effector , extracellular , enhancer , chemistry , gene , biochemistry , gene expression
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.