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Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b
P85α, which acts as a tumour suppressor, is frequently found to be downregulated in various human cancers. However, the role of p85α in the tumour microenvironment is unknown. Here, we report that aberrantly low expression of p85α in breast cancer stroma is clinically relevant to breast cancer disea...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562851/ https://www.ncbi.nlm.nih.gov/pubmed/28394344 http://dx.doi.org/10.1038/onc.2017.100 |
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author | Chen, Y Zeng, C Zhan, Y Wang, H Jiang, X Li, W |
author_facet | Chen, Y Zeng, C Zhan, Y Wang, H Jiang, X Li, W |
author_sort | Chen, Y |
collection | PubMed |
description | P85α, which acts as a tumour suppressor, is frequently found to be downregulated in various human cancers. However, the role of p85α in the tumour microenvironment is unknown. Here, we report that aberrantly low expression of p85α in breast cancer stroma is clinically relevant to breast cancer disease progression. Stromal fibroblasts can acquire the hallmarks of cancer-associated fibroblasts (CAFs) as a result of the loss of p85α expression. Paracrine Wnt10b from p85α-deficient fibroblasts can promote cancer progression via epithelial-to-mesenchymal transition (EMT) induced by the canonical Wnt pathway. Moreover, exosomes have a key role in paracrine Wnt10b transport from fibroblasts to breast cancer epithelial cells. Our results reveal that p85α expression in stromal fibroblasts haves a crucial role in regulating breast cancer tumourigenesis and progression by modifying stromal–epithelial crosstalk and remodelling the tumour microenvironment. Therefore, p85α can function as a tumour suppressor and represent a new candidate for diagnosis, prognosis and targeted therapy. |
format | Online Article Text |
id | pubmed-5562851 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Nature Publishing Group |
record_format | MEDLINE/PubMed |
spelling | pubmed-55628512017-08-24 Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b Chen, Y Zeng, C Zhan, Y Wang, H Jiang, X Li, W Oncogene Original Article P85α, which acts as a tumour suppressor, is frequently found to be downregulated in various human cancers. However, the role of p85α in the tumour microenvironment is unknown. Here, we report that aberrantly low expression of p85α in breast cancer stroma is clinically relevant to breast cancer disease progression. Stromal fibroblasts can acquire the hallmarks of cancer-associated fibroblasts (CAFs) as a result of the loss of p85α expression. Paracrine Wnt10b from p85α-deficient fibroblasts can promote cancer progression via epithelial-to-mesenchymal transition (EMT) induced by the canonical Wnt pathway. Moreover, exosomes have a key role in paracrine Wnt10b transport from fibroblasts to breast cancer epithelial cells. Our results reveal that p85α expression in stromal fibroblasts haves a crucial role in regulating breast cancer tumourigenesis and progression by modifying stromal–epithelial crosstalk and remodelling the tumour microenvironment. Therefore, p85α can function as a tumour suppressor and represent a new candidate for diagnosis, prognosis and targeted therapy. Nature Publishing Group 2017-08-17 2017-04-10 /pmc/articles/PMC5562851/ /pubmed/28394344 http://dx.doi.org/10.1038/onc.2017.100 Text en Copyright © 2017 The Author(s) http://creativecommons.org/licenses/by-nc-sa/4.0/ This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by-nc-sa/4.0/ |
spellingShingle | Original Article Chen, Y Zeng, C Zhan, Y Wang, H Jiang, X Li, W Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b |
title | Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b |
title_full | Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b |
title_fullStr | Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b |
title_full_unstemmed | Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b |
title_short | Aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine Wnt10b |
title_sort | aberrant low expression of p85α in stromal fibroblasts promotes breast cancer cell metastasis through exosome-mediated paracrine wnt10b |
topic | Original Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5562851/ https://www.ncbi.nlm.nih.gov/pubmed/28394344 http://dx.doi.org/10.1038/onc.2017.100 |
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