Fibronectin (FN)

Fibronectin (FN) is a large ∼500 to 600 kDa glycoprotein capable of binding to several different cell-surface integrins and ECM components, such as collagen, fibrin, and heparin. It mediates several cellular interactions with the extracellular matrix (ECM) and plays significant roles in cell adhesion, growth, migration, and differentiation. In humans, the FN1 gene provides instructions for synthesizing two types of FN proteins: soluble plasma fibronectin (pFN) and insoluble cellular fibronectin (cFN). Soluble pFN is produced in the liver by hepatocytes and secreted into the blood at a circulating concentration of ∼300 µg/mL, where it is mainly involved in blood clotting and wound healing. Upon tissue injury, pFN binds to platelets and fibrin, strengthening the fibrin clot and enhancing platelet adhesion, migration, and aggregation. Insoluble cFN is produced by various cell types, including fibroblasts, endothelial cells, chondrocytes, synovial cells, macrophages, and myocytes. It is first secreted as a soluble protein dimer and then converted to insoluble fibrillar matrices at the cell surfaces through a stepwise, cell-mediated process involving integrins and the cytoskeleton. These fibril networks are responsible for attaching cells to the ECM, controlling cell shape and migration during development, and supporting tissues. FN is encoded by the gene FN1, which has three regions susceptible to alternative splicing. Currently, 20 different FN isoforms have been identified.

Irregulations in FN expression, degradation, and organization have been widely implicated in the onset and progression of several pathologies, including cancer, fibronectin glomerulopathy, and spondylometaphyseal dysplasia. In non-small cell lung carcinoma development, overexpression of FN promotes tumorigenicity by enhancing the adhesion of lung carcinoma cells to FN and improves drug resistance.

References

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1. Pankov, R., & Yamada, K. M. (2002). Fibronectin at a glance. Journal of cell science, 115(Pt 20), 3861-3863. https://doi.org/10.1242/jcs.00059