期刊
JOURNAL OF EXTRACELLULAR VESICLES
卷 8, 期 1, 页码 -出版社
TAYLOR & FRANCIS LTD
DOI: 10.1080/20013078.2019.1690217
关键词
Exosomes; extracellular vesicles; colorectal cancer; proteomics; Wnt signalling; beta-catenin; tumour microenvironment
类别
资金
- Australian Research Council Discovery project grant [DP130100535]
- Australian Research Council DP [DP170102312]
- Australian Research Council FT [FT180100333]
- Ramaciotti Establishment Grant
- NIH Common Fund through the Office of Strategic Coordination/Office of the NIH Director [U54-DA036134]
- Victoria India Doctoral Scholarship from the Department of State Development, Business and Innovation (DSDBI)
- Australian Research Council [FT180100333] Funding Source: Australian Research Council
Mutations in beta-catenin, especially at the residues critical for its degradation, render it constitutively active. Here, we show that mutant beta-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 beta-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 beta-catenin. SILAC-based quantitative proteomics analysis confirmed the transfer of mutant beta-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 beta-catenin to the recipient cells and promote cancer progression.
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