Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
| Autor: | Jorge Barbazan, Manuel Gomez-Gonzalez, Marco Serra, Pascale Mariani, Carlos Pérez-González, Xavier Trepat, Dedenon M, Stéphanie Descroix, Sophie Richon, Pierre Sens, Latorre E, Danijela Matic Vignjevic |
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| Přispěvatelé: | Biologie Cellulaire et Cancer, Institut Curie [Paris]-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institute for Bioengineering of Catalonia [Barcelona] (IBEC), Laboratoire Physico-Chimie Curie [Institut Curie] (PCC), Institut Curie [Paris]-Institut de Chimie du CNRS (INC)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Institut Curie [Paris], Universitat de Barcelona (UB), Institució Catalana de Recerca i Estudis Avançats (ICREA), Centro de Investigación Biomédica en Red en Bioingeniería, Biomateriales y Nanomedicina (CIBER-BBN), Sens, Pierre |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0303 health sciences
biology Chemistry Cell biology Fibronectin Contractility Extracellular matrix 03 medical and health sciences 0302 clinical medicine [PHYS.COND.CM-GEN] Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other] In vivo Tumor progression 030220 oncology & carcinogenesis [PHYS.COND.CM-GEN]Physics [physics]/Condensed Matter [cond-mat]/Other [cond-mat.other] Cancer cell biology.protein Cancer-Associated Fibroblasts Mechanotransduction 030304 developmental biology |
| Popis: | During tumor progression, cancer-associated fibroblasts (CAFs) accumulate in tumors and produce excessive extracellular matrix (ECM), forming a capsule that enwraps cancer cells. This capsule is 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. Cancer cells mechanosense CAF compression, resulting in an altered localization of the transcriptional regulator YAP. 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. Our study unveils that the contractile capsule actively compresses cancer cells, modulates their mechanical signaling, and reorganizes tumor morphology. |
| Databáze: | OpenAIRE |
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