Role of cyclophilin a during oncogenesis.

Cyclophilins (Cyps) are ubiquitously expressed proteins that are evolutionarily conserved. CypA is the most abundant among the Cyps and is expressed in the cytosol. With its chaperone and PPIase activities, CypA contributes to the maintenance of correct conformation of nascent or denatured proteins and also provides protection against environmental insults. Also, its expression is induced in response to a wide variety of stressors including cancer. Upregulation of CypA in small cell lung cancer, pancreatic cancer, breast cancer, colorectal cancer, squamous cell carcinoma and melanoma has been reported. In some cancers a correlation between CypA overexpression and malignant transformation has been established. While molecular partners of CypA that promote cancer development are yet to be discovered, various mechanisms have been proposed to account for the cytoprotective functions of CypA during cancer development. CypA may promote the survival of cells under the stressful condition of cancer. CypA may well be essential for maintaining the conformation of oncogenic proteins, signalling proteins for cell proliferation, antiapoptotic components, transcription factors, or cell motility regulatory proteins. Antioxidant effects of CypA, which have been suggested by some researchers, may also become critical to reactive oxygen species (ROS) creating an oncogenetic environment. Developing new CypA inhibitors for therapeutics has been surmised from the cytoprotective functions of CypA and its overexpression in many cancer types. Therefore, CypA can be further investigated as a useful tool for early diagnosis, treatment and prevention of human cancers.