Journal article
Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells
H Kalra, L Gangoda, P Fonseka, SV Chitti, M Liem, S Keerthikumar, M Samuel, S Boukouris, H Al Saffar, C Collins, CG Adda, CS Ang, S Mathivanan
Journal of Extracellular Vesicles | TAYLOR & FRANCIS LTD | Published : 2019
Open access
Abstract
Mutations in β-catenin, especially at the residues critical for its degradation, render it constitutively active. Here, we show that mutant β-catenin can be transported via extracellular vesicles (EVs) and activate Wnt signalling pathway in the recipient cells. An integrative proteogenomic analysis identified the presence of mutated β-catenin in EVs secreted by colorectal cancer (CRC) cells. Follow-up experiments established that EVs released from LIM1215 CRC cells stimulated Wnt signalling pathway in the recipient cells with wild-type β-catenin. SILAC-based quantitative proteomics analysis confirmed the transfer of mutant β-catenin to the nucleus of the recipient cells. In vivo tracking of ..
View full abstractGrants
Awarded by National Institutes of Health
Funding Acknowledgements
SM is supported by Australian Research Council Discovery project grant (Grant number DP130100535), Australian Research Council DP (Grant number DP170102312), Australian Research Council FT (Grant number FT180100333), Ramaciotti Establishment Grant and Award U54-DA036134 supported by the NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director. HK is supported by a Victoria India Doctoral Scholarship from the Department of State Development, Business and Innovation (DSDBI). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.