Thioredoxin and thioredoxin-binding protein-2 in cancer and metabolic syndrome

Abstract

Thioredoxin (TRX), a small redox-active multifunctional protein, acts as a potent antioxidant and a redox regulator in signal transduction. TRX expression is elevated in various types of human cancer. Overexpression of TRX introduces resistance to anti-cancer drugs or radiation-induced apoptosis; however, there is no evidence that the incidence of cancer is frequent in TRX-transgenic mice or that the administration of recombinant human TRX enhances tumor growth. Plasma/serum level of TRX is a good marker for oxidative stress-induced various disorders, including metabolic syndrome. Thioredoxin-binding protein-2 (TBP-2), which was originally identified as a negative regulator of TRX, acts as a growth suppressor and a regulator in lipid metabolism. TBP-2 expression is downregulated in various types of human cancer. TBP-2 deficiency induces lipid dysfunction and a phenotype resembling Reye syndrome. Thus, TRX and TBP-2 play important roles in the pathophysiology of cancer and metabolic syndrome by direct interaction or by independent mechanisms.