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Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells

The pHs of extracellular fluids (ECFs) in normal tissues are commonly maintained at 7.35 to 7.45. The acidification of the ECF is one of the major characteristics of tumour microenvironment. In this study, we report that decreased extracellular pH promotes the transformation of mesenchymal stem cell...

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Autores principales: Zhu, Hongyi, Guo, Shangchun, Zhang, Yuelei, Yin, Junhui, Yin, Wenjing, Tao, Shicong, Wang, Yang, Zhang, Changqing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Ivyspring International Publisher 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807159/
https://www.ncbi.nlm.nih.gov/pubmed/27019624
http://dx.doi.org/10.7150/ijbs.13688
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author Zhu, Hongyi
Guo, Shangchun
Zhang, Yuelei
Yin, Junhui
Yin, Wenjing
Tao, Shicong
Wang, Yang
Zhang, Changqing
author_facet Zhu, Hongyi
Guo, Shangchun
Zhang, Yuelei
Yin, Junhui
Yin, Wenjing
Tao, Shicong
Wang, Yang
Zhang, Changqing
author_sort Zhu, Hongyi
collection PubMed
description The pHs of extracellular fluids (ECFs) in normal tissues are commonly maintained at 7.35 to 7.45. The acidification of the ECF is one of the major characteristics of tumour microenvironment. In this study, we report that decreased extracellular pH promotes the transformation of mesenchymal stem cells (MSCs) into cancer-associated fibroblasts (CAFs), termed CAF activation. Furthermore, we demonstrate that GPR68, a proton-sensing G-protein-coupled receptor (GPCR), is required for the pH-dependent regulation of the differentiation of MSCs into CAFs. We then identify Yes-associated protein 1 (YAP) as a downstream effector of GPR68 for CAF activation. Finally, we show that knockdown of GPR68 in MSCs can prevent the CAF activation under cancer microenvironment. Systemic transplantation of GPR68-silenced MSCs suppresses in-situ tumour growth and prolong life span after cancer graft.
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spelling pubmed-48071592016-03-25 Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells Zhu, Hongyi Guo, Shangchun Zhang, Yuelei Yin, Junhui Yin, Wenjing Tao, Shicong Wang, Yang Zhang, Changqing Int J Biol Sci Research Paper The pHs of extracellular fluids (ECFs) in normal tissues are commonly maintained at 7.35 to 7.45. The acidification of the ECF is one of the major characteristics of tumour microenvironment. In this study, we report that decreased extracellular pH promotes the transformation of mesenchymal stem cells (MSCs) into cancer-associated fibroblasts (CAFs), termed CAF activation. Furthermore, we demonstrate that GPR68, a proton-sensing G-protein-coupled receptor (GPCR), is required for the pH-dependent regulation of the differentiation of MSCs into CAFs. We then identify Yes-associated protein 1 (YAP) as a downstream effector of GPR68 for CAF activation. Finally, we show that knockdown of GPR68 in MSCs can prevent the CAF activation under cancer microenvironment. Systemic transplantation of GPR68-silenced MSCs suppresses in-situ tumour growth and prolong life span after cancer graft. Ivyspring International Publisher 2016-02-05 /pmc/articles/PMC4807159/ /pubmed/27019624 http://dx.doi.org/10.7150/ijbs.13688 Text en © Ivyspring International Publisher. Reproduction is permitted for personal, noncommercial use, provided that the article is in whole, unmodified, and properly cited. See http://ivyspring.com/terms for terms and conditions.
spellingShingle Research Paper
Zhu, Hongyi
Guo, Shangchun
Zhang, Yuelei
Yin, Junhui
Yin, Wenjing
Tao, Shicong
Wang, Yang
Zhang, Changqing
Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells
title Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells
title_full Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells
title_fullStr Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells
title_full_unstemmed Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells
title_short Proton-sensing GPCR-YAP Signalling Promotes Cancer-associated Fibroblast Activation of Mesenchymal Stem Cells
title_sort proton-sensing gpcr-yap signalling promotes cancer-associated fibroblast activation of mesenchymal stem cells
topic Research Paper
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4807159/
https://www.ncbi.nlm.nih.gov/pubmed/27019624
http://dx.doi.org/10.7150/ijbs.13688
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