Extracellular vesicles containing oncogenic mutant β-catenin activate Wnt signalling pathway in the recipient cells

被引：69

作者：

Kalra, Hina ^{[1
]}

Gangoda, Lahiru ^{[1
]}

Fonseka, Pamali ^{[1
]}

Chitti, Sai, V ^{[1
]}

Liem, Michael ^{[1
]}

Keerthikumar, Shivakumar ^{[1
,2
,3
]}

Samuel, Monisha ^{[1
]}

Boukouris, Stephanie ^{[1
]}

Al Saffar, Haidar ^{[1
]}

Collins, Christine ^{[1
]}

Adda, Christopher G. ^{[1
]}

Ang, Ching-Seng ^{[4
]}

Mathivanan, Suresh ^{[1
]}

机构：

[1] La Trobe Univ, La Trobe Inst Mol Sci, Dept Biochem & Genet, Melbourne, Vic, Australia

[2] Peter MacCallum Canc Ctr, Canc Res Div, Melbourne, Vic, Australia

[3] Univ Melbourne, Sir Peter MacCallum Dept Oncol, Melbourne, Vic, Australia

[4] Univ Melbourne, Bio21 Mol Sci & Biotechnol Inst, Parkville, Vic, Australia

来源：

JOURNAL OF EXTRACELLULAR VESICLES | 2019年 / 8卷 / 01期

基金：

澳大利亚研究理事会;

关键词：

Exosomes; extracellular vesicles; colorectal cancer; proteomics; Wnt signalling; beta-catenin; tumour microenvironment; MESENCHYMAL STEM-CELLS; BREAST-CANCER CELLS; COLORECTAL-CANCER; HUMAN COLON; IFN-GAMMA; EXOSOMES; HETEROGENEITY; MUTATIONS; MICROVESICLES; STROMA;

D O I：

10.1080/20013078.2019.1690217

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

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.

引用

页数：13

共 40 条

[1]

Intercellular transfer of the oncogenic receptor EGFrvIII by microvesicles derived from tumour cells [J].