Fibronectin

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Fibronectin 1
Identifiers
Symbol	FN1
HUGO	3778
Entrez	2335
OMIM	135600
RefSeq	NM_002026
UniProt	P02751
Other data
Locus	Chr. 2 q34-q36

Fibronectin is a high-molecular-weight glycoprotein containing about 5% carbohydrate that binds to receptor proteins that span the cell's membrane, called integrins. In addition to integrins, they also bind extracellular matrix components such as collagen, fibrin and heparin.

Fibronectin can be found in the blood plasma in its soluble form which is composed of two 250 kDa subunits joined together by disulfide bonds. Plasma fibronectin is made in the liver by hepatocytes. The insoluble form that was formerly called cold-insoluble globulin is a large complex of cross-linked subunits.

There are several isoforms of fibronectin all of which are the product of a single gene. The structure of these isoforms are made of three types of repeated internal regions called I, II and III which exhibit different lengths and presence or absence of disulfide bonds. Alternative splicing of the Pre-mRNA leads to the combination of these three types of regions but also to a variable region.

Fibronectin is involved in the wound healing process and so can be used as a therapeutic agent. It is also one of the few proteins for which production increases with age without any associated pathology. Fibronectin is also found in normal human saliva, which helps prevent colonization of the oral cavity and pharynx by potentially pathogenic bacteria.

1 Fibronectin and Cancer
2 Structure of Fibronectin
3 Functions of Fibronectin
4 References
5 External links

Fibronectin has been implicated in carcinoma development.^[1] 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 induced by standard chemotherapeutic agents. Fibronectin has been shown to stimulate the phosphatidylinositol 3-kinase (PI3K), which is capable of controlling the expression of cyclin D and related genes involved in cell cycle control. This suggests that fibronectin promotes lung tumor growth/survival and resistance to therapy and could represent a novel target for the development of new anticancer drugs.

Fibronectin is composed of two similar polypeptide chains of approximately 30 modules. These polypeptide chains are attached by disulfide bridges, and are folded into a linear series of 5 or 6 functional units. These functional units contain interaction sites for other Extracellular components or cell surface molecules.

Other than the ones stated previously, Fibronectin has numerous functions that ensure the normal funtioning of life. One of its more notable functions is its role as a 'guide' in cellular migration pathways in mammalian development, particularily the Neural Crest (ectoderm cells that will develop into skin pigment cells as well as some bones of the skull). Fibronectin helps maintain the shape of cells by lining up and organizing intracellular cytoskeleton by means of receptors. It helps stabilize the attachment of ECM (Extracellular matrix) to cells by acting as binding sites for cell surface receptors. More generally though, Fibronectin helps create a cross-linked network within the Extracellular Matrix by having binding sites for other ECM components.

^ Han S, Khuri F, Roman J (2006). "Fibronectin stimulates non-small cell lung carcinoma cell growth through activation of Akt/mammalian target of rapamycin/S6 kinase and inactivation of LKB1/AMP-activated protein kinase signal pathways". Cancer Res 66 (1): 315-23. PMID 16397245.