title: Biomechanical remodeling of the microenvironment by stromal caveolin-1 favors tumor invasion and metastasis.
abstract: Mechanotransduction is a key determinant of tissue homeostasis and tumor progression. It is driven by intercellular adhesions, cell contractility, and forces generated within the microenvironment and is dependent on extracellular matrix composition, organization, and compliance. We show that caveolin-1 (Cav1) favors cell elongation in three-dimensional cultures and promotes Rho- and force-dependent contraction, matrix alignment, and microenvironment stiffening through regulation of p190RhoGAP. In turn, microenvironment remodeling by Cav1 fibroblasts forces cell elongation. Cav1-deficient mice have disorganized stromal tissue architecture. Stroma associated with human carcinomas and melanoma metastases is enriched in Cav1-expressing carcinoma-associated fibroblasts (CAFs). Cav1 expression in breast CAFs correlates with low survival, and Cav1 depletion in CAFs decreases CAF contractility. Consistently, fibroblast expression of Cav1, through p190RhoGAP regulation, favors directional migration and invasiveness of carcinoma cells in vitro. In vivo, stromal Cav1 remodels peri- and intratumoral microenvironments to facilitate tumor invasion, correlating with increased metastatic potency. Thus, Cav1 modulates tissue responses through force-dependent architectural regulation of the microenvironment.
authors: Integrin Signaling Laboratory, Department of Vascular Biology and Inflammation, Centro Nacional de Investigaciones Cardiovasculares (CNIC), Madrid 28029, Spain. jgoetz@igbmc.fr
authors: Jacky G
authors: JG
authors: Goetz
authors: Susana
authors: S
authors: Minguet
authors: Inmaculada
authors: I
authors: Navarro-Lérida
authors: Juan José
authors: JJ
authors: Lazcano
authors: Rafael
authors: R
authors: Samaniego
authors: Enrique
authors: E
authors: Calvo
authors: Marta
authors: M
authors: Tello
authors: Teresa
authors: T
authors: Osteso-Ibáñez
authors: Teijo
authors: T
authors: Pellinen
authors: Asier
authors: A
authors: Echarri
authors: Ana
authors: A
authors: Cerezo
authors: Andres J P
authors: AJ
authors: Klein-Szanto
authors: Ricardo
authors: R
authors: Garcia
authors: Patricia J
authors: PJ
authors: Keely
authors: Paloma
authors: P
authors: Sánchez-Mateos
authors: Edna
authors: E
authors: Cukierman
authors: Miguel A
authors: MA
authors: Del Pozo
mesh_terms: D000818:Animals; D051242:Caveolin 1 / Q000378:metabolism*; D002465:Cell Movement; D005347:Fibroblasts / Q000473:pathology; D006801:Humans; D008545:Melanoma / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D009362:Neoplasm Metastasis / Q000473:pathology*; D009369:Neoplasms / Q000473:pathology*
chemical_list: D051242:Caveolin 1