Tagged: Fibronectin


Fibronectin is a high-molecular weight  glycoprotein of the extracellular matrix that binds to membrane-spanning receptor proteinscalled integrins Similar to integrins, fibronectin binds extracellular matrix components such as collagen, fibrin, and heparan sulfateproteoglycans (e.g. syndecans).

Fibronectin exists as a protein dimer, consisting of two nearly identical monomers linked by a pair of disulfide bonds. The fibronectin protein is produced from a single gene, but alternative splicing of its pre-mRNA leads to the creation of several isoforms.

Two types of fibronectin are present in vertebrates:

  • soluble plasma fibronectin (formerly called “cold-insoluble globulin”, or CIg) is a major protein component of blood plasma (300 μg/ml) and is produced in the liver by hepatocytes.
  • insoluble cellular fibronectin is a major component of the extracellular matrix. It is secreted by various cells, primarily fibroblasts, as a soluble protein dimer and is then assembled into an insoluble matrix in a complex cell-mediated process.

Fibronectin plays a major role in cell adhesion, growth, migration, and differentiation, and it is important for processes such as wound healingand embryonic development. Altered fibronectin expression, degradation, and organization has been associated with a number ofpathologies, including cancer and fibrosis.

Fibronectin has numerous functions that ensure the normal functioning of vertebrate organisms.[1] It is involved in cell adhesion, growth,migration, and differentiation. Cellular fibronectin is assembled into the extracellular matrix, an insoluble network that separates and supports the organs and tissues of an organism.

Fibronectin plays a crucial role in wound healing. Along with fibrin, plasma fibronectin is deposited at the site of injury, forming a blood clot that stops bleeding and protects the underlying tissue. As repair of the injured tissue continues, fibroblasts and macrophages begin to remodel the area, degrading the proteins that form the provisional blood clot matrix and replacing them with a matrix that more resembles the normal, surrounding tissue. Fibroblasts secrete proteases, including matrix metalloproteinases, that digest the plasma fibronectin, and then the fibroblasts secrete cellular fibronectin and assemble it into an insoluble matrix. Fragmentation of fibronectin by proteases has been suggested to promote wound contraction, a critical step in wound healing. Fragmenting fibronectin further exposes its V-region, which contains the site for α4β1 integrin-binding. These fragments of fibronectin are believed to enhance α4β1 integrins-expressing cell binding, allowing them to adhere to and forcefully contract the surrounding matrix.

Fibronectin is necessary for embryogenesis, and inactivating the gene for fibronectin results in early embryonic lethality.Fibronectin is important for guiding cell attachment and migration during embryonic development. In mammalian development, the absence of fibronectin leads to defects in mesodermal, neural tube, and vascular development. Similarly, the absence of a normal fibronectin matrix in developing amphibians causes defects in mesodermal patterning and inhibits gastrulation.

Fibronectin is also found in normal human saliva, which helps prevent colonization of the oral cavity and pharynx by potentially pathogenic bacteria.
Several of the morphological changes observed in tumors and tumor-derived cell lines have been attributed to decreased fibronectin expression, increased fibronectin degradation, and/or decreasedexpression of fibronectin-binding receptors, such as α5β1 integrins.
Fibronectin has been implicated in carcinoma development. In lung carcinoma, fibronectin expression is increased, especially in non-small cell lung carcinoma. The adhesion of lung carcinoma cells to fibronectin enhances tumorigenicity and confers resistance to apoptosis-inducing chemotherapeutic agents. Fibronectin has been shown to stimulate the gonadal steroids that interact withvertebrate androgen receptors, which are capable of controlling the expression of cyclin D and related genes involved in cell cycle control. These observations suggest that fibronectin may promote lung tumor growth/survival and resistance to therapy, and it could represent a novel target for the development of new anticancer drugs.
Fibronectin 1 acts as a potential biomarker for radio resistance.