Biomechanical remodeling of the microenvironment by stromal Caveolin-1 favors tumor invasion and metastasis

By J. Goetz, S. Minguet, Inmaculada Navarro-Lérida, J. J. Lazcano, R. Samaniego, E. Calvo, M. Tello, T. Osteso-Ibáñez, T. Pellinen, A. Echarri and 7 more. Cell, 2011

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Summary Mechanotransduction, a key determinant of tissue homeostasis and tumor progression, is driven by intercellular adhesions, cell contractility and forces generated with the microenvironment, dependent on extracellular matrix composition, organization and compliance. Caveolin-1 (Cav1) favors cell elongation in 3D 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.

Subfields: Cell Biology, Molecular Biology

View Paper: https://www.semanticscholar.org/paper/8c3371d2a211da6fa0f5bc367e56fcdea4f14057

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Citations in the corpus

Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance (2019, background): “The ensuing remodeling of the tumor stroma favors directional migration, invasion, and metastasis (Goetz et al., 2011).”
Exosomes mediate stromal mobilization of autocrine Wnt-PCP signaling in breast cancer cell migration. (2012, background): “Moreover, ECM remodeling by CAFs 1542 Cell 151, 1542–1556, December 21, 2012 ª2012 Elsevier Inc. is essential for tumor cell invasion and metastasis (Gaggioli et al., 2007; Goetz et al., 2011).”
Causes, consequences, and remedies for growth-induced solid stress in murine and human tumors (2012, background): “Indeed, increased tumor tissue stiffness has been linked to tumor incidence and progression (59, 60).”
Cancer invasion and the microenvironment: plasticity and reciprocity. (2011, positive): “generates micro- and macrotracks bordered by condensed ordered collagen bundles, which strongly support both singlecell and collective invasion (Friedl et al., 1997; Gaggioli et al., 2007; Goetz et al., 2011; Wolf et al., 2007) (Figure 5A).”
Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer. (2018, neutral): “Finally, the clinical significance of either CAV1 or FSP1 expression in stroma has been demonstrated in BC, although with some conflicting information on patient survival (Rudland et al., 2000; Lee et al., 2004; Goetz et al., 2011; Simpkins et al., 2012).”
Fibroblast heterogeneity in the cancer wound (2014, background): “Rho-dependent cytoskeletal remodeling in CAFs was shown to be activated by Palladin, Cav-1, or JAK signaling cascades, and led to Actomyosin contractility and enhanced invasion (Hooper et al., 2010; Goetz et al., 2011; Sanz-Moreno et al., 2011; Brentnall et al., 2012).”
Characteristics and Significance of the Pre-metastatic Niche. (2016, background): “CD105-positive microvesicles released from human renal cancer stem cells also stimulate the angiogenesis by conferring an activated angiogenic phenotype to normal human endothelial cells for lung pre-metastatic niche formation, which significantly promotes lung metastasis (Grange et al., 2011).”