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Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics
Both the MRTF–SRF and the YAP–TEAD transcriptional regulatory networks respond to extracellular signals and mechanical stimuli. We show that the MRTF–SRF pathway is activated in cancer-associated fibroblasts (CAFs). The MRTFs are required in addition to the YAP pathway for CAF contractile and proinv...
Autores principales: | , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Cold Spring Harbor Laboratory Press
2017
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795783/ https://www.ncbi.nlm.nih.gov/pubmed/29317486 http://dx.doi.org/10.1101/gad.304501.117 |
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author | Foster, Charles T. Gualdrini, Francesco Treisman, Richard |
author_facet | Foster, Charles T. Gualdrini, Francesco Treisman, Richard |
author_sort | Foster, Charles T. |
collection | PubMed |
description | Both the MRTF–SRF and the YAP–TEAD transcriptional regulatory networks respond to extracellular signals and mechanical stimuli. We show that the MRTF–SRF pathway is activated in cancer-associated fibroblasts (CAFs). The MRTFs are required in addition to the YAP pathway for CAF contractile and proinvasive properties. We compared MRTF–SRF and YAP–TEAD target gene sets and identified genes directly regulated by one pathway, the other, or both. Nevertheless, the two pathways exhibit mutual dependence. In CAFs, expression of direct MRTF–SRF genomic targets is also dependent on YAP–TEAD activity, and, conversely, YAP–TEAD target gene expression is also dependent on MRTF–SRF signaling. In normal fibroblasts, expression of activated MRTF derivatives activates YAP, while activated YAP derivatives activate MRTF. Cross-talk between the pathways requires recruitment of MRTF and YAP to DNA via their respective DNA-binding partners (SRF and TEAD) and is therefore indirect, arising as a consequence of activation of their target genes. In both CAFs and normal fibroblasts, we found that YAP–TEAD activity is sensitive to MRTF–SRF-induced contractility, while MRTF–SRF signaling responds to YAP–TEAD-dependent TGFβ signaling. Thus, the MRF–SRF and YAP–TEAD pathways interact indirectly through their ability to control cytoskeletal dynamics. |
format | Online Article Text |
id | pubmed-5795783 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2017 |
publisher | Cold Spring Harbor Laboratory Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-57957832018-02-05 Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics Foster, Charles T. Gualdrini, Francesco Treisman, Richard Genes Dev Research Paper Both the MRTF–SRF and the YAP–TEAD transcriptional regulatory networks respond to extracellular signals and mechanical stimuli. We show that the MRTF–SRF pathway is activated in cancer-associated fibroblasts (CAFs). The MRTFs are required in addition to the YAP pathway for CAF contractile and proinvasive properties. We compared MRTF–SRF and YAP–TEAD target gene sets and identified genes directly regulated by one pathway, the other, or both. Nevertheless, the two pathways exhibit mutual dependence. In CAFs, expression of direct MRTF–SRF genomic targets is also dependent on YAP–TEAD activity, and, conversely, YAP–TEAD target gene expression is also dependent on MRTF–SRF signaling. In normal fibroblasts, expression of activated MRTF derivatives activates YAP, while activated YAP derivatives activate MRTF. Cross-talk between the pathways requires recruitment of MRTF and YAP to DNA via their respective DNA-binding partners (SRF and TEAD) and is therefore indirect, arising as a consequence of activation of their target genes. In both CAFs and normal fibroblasts, we found that YAP–TEAD activity is sensitive to MRTF–SRF-induced contractility, while MRTF–SRF signaling responds to YAP–TEAD-dependent TGFβ signaling. Thus, the MRF–SRF and YAP–TEAD pathways interact indirectly through their ability to control cytoskeletal dynamics. Cold Spring Harbor Laboratory Press 2017-12-01 /pmc/articles/PMC5795783/ /pubmed/29317486 http://dx.doi.org/10.1101/gad.304501.117 Text en © 2018 Foster et al.; Published by Cold Spring Harbor Laboratory Press http://creativecommons.org/licenses/by/4.0/ This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/. |
spellingShingle | Research Paper Foster, Charles T. Gualdrini, Francesco Treisman, Richard Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics |
title | Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics |
title_full | Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics |
title_fullStr | Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics |
title_full_unstemmed | Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics |
title_short | Mutual dependence of the MRTF–SRF and YAP–TEAD pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics |
title_sort | mutual dependence of the mrtf–srf and yap–tead pathways in cancer-associated fibroblasts is indirect and mediated by cytoskeletal dynamics |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5795783/ https://www.ncbi.nlm.nih.gov/pubmed/29317486 http://dx.doi.org/10.1101/gad.304501.117 |
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