FGA (Fibrinogen α)

Function

Fibrinogen is a 340 kDa hexamer of two each of three chains (α, β, γ), made by the liver and circulating at 2-4 g/L - the third-highest plasma protein concentration. Thrombin cleaves short peptides from the α and β chains, the molecules polymerize into fibrin strands, and Factor XIII cross-links them into the mesh that stops bleeding. The acute-phase response raises fibrinogen several-fold (IL-6 drives hepatic production), which is why fibrinogen is a clinical inflammation marker. Fibrin is also the provisional scaffold of wound healing, binding growth factors and providing the matrix through which cells migrate during repair.

In cancer

Tumors co-opt the clotting system. Fibrin deposits form in and around tumors, where they scaffold stromal cells, shelter tumor cells from immune attack, and promote platelet aggregation - the mechanism behind the elevated thrombosis risk in cancer patients (Trousseau’s syndrome). Fibrinogen and fibrin also promote metastatic seeding: circulating tumor cells caught in fibrin deposits arrest in capillaries and extravasate more efficiently. Fibrinogen α-chain is itself expressed by some gliomas as a fusion transcript (FGFR3-TACC3 is a separate event; glioma fibrinogen expression is ectopic).

Notes

• Human gene symbol: FGA; UniProt P02671; 866 amino acids (precursor); fibrinogen α chain.