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Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells
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...
Autores principales: | , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Taylor & Francis
2019
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883417/ https://www.ncbi.nlm.nih.gov/pubmed/31819794 http://dx.doi.org/10.1080/20013078.2019.1690217 |
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author | 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 |
author_facet | 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 |
author_sort | Kalra, Hina |
collection | PubMed |
description | 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. |
format | Online Article Text |
id | pubmed-6883417 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2019 |
publisher | Taylor & Francis |
record_format | MEDLINE/PubMed |
spelling | pubmed-68834172019-12-09 Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells 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 J Extracell Vesicles Research Article 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. Taylor & Francis 2019-11-15 /pmc/articles/PMC6883417/ /pubmed/31819794 http://dx.doi.org/10.1080/20013078.2019.1690217 Text en © 2019 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group on behalf of The International Society for Extracellular Vesicles. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Research Article 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 Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells |
title | Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells |
title_full | Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells |
title_fullStr | Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells |
title_full_unstemmed | Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells |
title_short | Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells |
title_sort | extracellular vesicles containing oncogenic mutant β-catenin activate wnt signalling pathway in the recipient cells |
topic | Research Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883417/ https://www.ncbi.nlm.nih.gov/pubmed/31819794 http://dx.doi.org/10.1080/20013078.2019.1690217 |
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