PT  - JOURNAL ARTICLE
AU  - Jorge Barbazan
AU  - Carlos Pérez-González
AU  - Manuel Gómez-González
AU  - Mathieu Dedenon
AU  - Sophie Richon
AU  - Ernest Latorre
AU  - Marco Serra
AU  - Pascale Mariani
AU  - Stéphanie Descroix
AU  - Pierre Sens
AU  - Xavier Trepat
AU  - Danijela Matic Vignjevic
TI  - Cancer-associated fibroblasts actively compress cancer cells and modulate mechanotransduction
AID  - 10.1101/2021.04.05.438443
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.04.05.438443
4099  - http://biorxiv.org/content/early/2021/04/05/2021.04.05.438443.short
4100  - http://biorxiv.org/content/early/2021/04/05/2021.04.05.438443.full
AB  - 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.Competing Interest StatementThe authors have declared no competing interest.