Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells. Issue 1 (1st December 2019)

• Record Type: Journal Article
• Authors: Kalra, Hina; Gangoda, Lahiru; Fonseka, Pamali; Chitti, Sai V.; Liem, Michael; Keerthikumar, Shivakumar; Samuel, Monisha; Boukouris, Stephanie; Al Saffar, Haidar; Collins, Christine; Adda, Christopher G.; Ang, Ching-Seng; Mathivanan, Suresh
• Is Part Of: Journal of extracellular vesicles. Volume 8:Issue 1(2019)
• Publication Date: 2019-12-01
• Subjects: Exosomes -- extracellular vesicles -- colorectal cancer -- proteomics -- Wnt signalling -- β-catenin -- tumour microenvironment; Cells -- Mechanical properties -- Periodicals; Transport Vesicles; Cells -- Mechanical properties; Periodicals; Fulltext; Internet Resources; Periodicals; Electronic journals; Periodicals; 571.63
• DOI: 10.1080/20013078.2019.1690217
• Languages: English
• ISSNs: 2001-3078

Abstract

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 DiR-labelled EVs in mouse implanted with RKO CRC cells revealed its bio-distribution, confirmed the activation of Wnt signalling pathway in tumour cells and increased the tumour burden. Overall, for the first time, this study reveals that EVs can transfer mutant β-catenin to the recipient cells and promote cancer progression.