“…FN can affect VEGFA/VEGFR2 signaling by binding and organizing VEGFA. 41 , 42 Immunofluorescence results showed that FN and VEGFA were co-localized in large vessels and peripheral liver sinusoids ( Figure 5 F). Figure 5 Altered liver ECM compositions in Adamts18 -/- livers (A) Upper panel: representative immunohistochemistry images of fibronectin (FN) in 2-week-old mouse livers.…”
“…FN can affect VEGFA/VEGFR2 signaling by binding and organizing VEGFA. 41 , 42 Immunofluorescence results showed that FN and VEGFA were co-localized in large vessels and peripheral liver sinusoids ( Figure 5 F). Figure 5 Altered liver ECM compositions in Adamts18 -/- livers (A) Upper panel: representative immunohistochemistry images of fibronectin (FN) in 2-week-old mouse livers.…”
“…Fibronectin is a critical matrix component associated with sprouting angiogenesis. 66 It is essential for tip cell migration 67 and filopodia formation. 68 Blocking fibronectin disrupts angiogenesis.…”
“…It is well established that GFs bound to FN retain the ability to bind to their respective receptors. Usuelli et al (2021) demonstrated that FN provides interaction motifs to the extracellular domain of the VEGF receptor 2 (VEGFR2), akin to the VEGF-binding sites that were also exposed upon heparin-induced conformational changes in FN. This suggests that a triple complex formation could occur, initiated either by VEGF or VEGFR2 binding to FN, followed by the recruitment of the third binding partner, thereby activating angiogenic signaling pathways.…”
Section: The Fn Hepii Region Binds Growth Factorsmentioning
The extracellular matrix (ECM) is a complex network of proteins and glycans, dynamically remodeled and specifically tailored to the structure/function of each organ. The malignant transformation of cancer cells is determined by both cell intrinsic properties, such as mutations, and extrinsic variables, such as the mixture of surrounding cells in the tumor microenvironment and the biophysics of the ECM. During cancer progression, the ECM undergoes extensive remodeling, characterized by disruption of the basal lamina, vascular endothelial cell invasion, and development of fibrosis in and around the tumor cells resulting in increased tissue stiffness. This enhanced rigidity leads to aberrant mechanotransduction and further malignant transformation potentiating the de-differentiation, proliferation and invasion of tumor cells. Interestingly, this fibrotic microenvironment is primarily secreted and assembled by non-cancerous cells. Among them, the cancer-associated fibroblasts (CAFs) play a central role. CAFs massively produce fibronectin together with type I collagen. This review delves into the primary interactions and signaling pathways through which fibronectin can support tumorigenesis and metastasis, aiming to provide critical molecular insights for better therapy response prediction.
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