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Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction

During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining...

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Autores principales: Barbazan, Jorge, Pérez-González, Carlos, Gómez-González, Manuel, Dedenon, Mathieu, Richon, Sophie, Latorre, Ernest, Serra, Marco, Mariani, Pascale, Descroix, Stéphanie, Sens, Pierre, Trepat, Xavier, Vignjevic, Danijela Matic
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618488/
https://www.ncbi.nlm.nih.gov/pubmed/37907483
http://dx.doi.org/10.1038/s41467-023-42382-4
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author Barbazan, Jorge
Pérez-González, Carlos
Gómez-González, Manuel
Dedenon, Mathieu
Richon, Sophie
Latorre, Ernest
Serra, Marco
Mariani, Pascale
Descroix, Stéphanie
Sens, Pierre
Trepat, Xavier
Vignjevic, Danijela Matic
author_facet Barbazan, Jorge
Pérez-González, Carlos
Gómez-González, Manuel
Dedenon, Mathieu
Richon, Sophie
Latorre, Ernest
Serra, Marco
Mariani, Pascale
Descroix, Stéphanie
Sens, Pierre
Trepat, Xavier
Vignjevic, Danijela Matic
author_sort Barbazan, Jorge
collection PubMed
description During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology.
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spelling pubmed-106184882023-11-02 Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction Barbazan, Jorge Pérez-González, Carlos Gómez-González, Manuel Dedenon, Mathieu Richon, Sophie Latorre, Ernest Serra, Marco Mariani, Pascale Descroix, Stéphanie Sens, Pierre Trepat, Xavier Vignjevic, Danijela Matic Nat Commun Article During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce an excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule acts as a barrier that restricts tumor growth leading to the buildup of intratumoral pressure. Combining genetic and physical manipulations in vivo with microfabrication and force measurements in vitro, we found that the CAFs capsule is not a passive barrier but instead actively compresses cancer cells using actomyosin contractility. Abrogation of CAFs contractility in vivo leads to the dissipation of compressive forces and impairment of capsule formation. By mapping CAF force patterns in 3D, we show that compression is a CAF-intrinsic property independent of cancer cell growth. Supracellular coordination of CAFs is achieved through fibronectin cables that serve as scaffolds allowing force transmission. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP and a decrease in proliferation. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology. Nature Publishing Group UK 2023-11-01 /pmc/articles/PMC10618488/ /pubmed/37907483 http://dx.doi.org/10.1038/s41467-023-42382-4 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Barbazan, Jorge
Pérez-González, Carlos
Gómez-González, Manuel
Dedenon, Mathieu
Richon, Sophie
Latorre, Ernest
Serra, Marco
Mariani, Pascale
Descroix, Stéphanie
Sens, Pierre
Trepat, Xavier
Vignjevic, Danijela Matic
Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
title Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
title_full Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
title_fullStr Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
title_full_unstemmed Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
title_short Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
title_sort cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10618488/
https://www.ncbi.nlm.nih.gov/pubmed/37907483
http://dx.doi.org/10.1038/s41467-023-42382-4
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