An Overview of Cyclophilins in Human Cancers

Cyclophilins (Cyps) belong to a group of proteins that have peptidyl-prolyl cis-trans isomerase (PPIase) and molecular chaperone activities. Originally, Cyps were identified as the intracellular receptors for the immunosuppressive drug cyclosporin A. Cyps are found in all prokaryotes and eukaryotes, and have been structurally conserved throughout evolution, implying their importance in cellular function. There are seven major Cyp isoforms in humans. CypA is up-regulated in many human cancers, and there is a strong correlation between over-expression of the CYPA gene and malignant transformation in some cancers. Moreover, CypA is directly under the transcriptional control of two critical transcription factors for cancer development: p53 and hypoxia inducible factor-la. This review discusses the general biological functions of Cyps under a variety of stress conditions, and the importance and diverse roles of overexpression of CYP genes in human cancers, with a particular emphasis on CYPA. These oncogenic properties suggest that CypA is a promising target for cancer therapy.