Multidisciplinary Analysis of Cyclophilin a Function in Human Breast Cancer

摘要

The major goal of the proposed project is to understand how cyclophilin A (CypA) modulates the prolactin (PRL) receptor (PRLr)-associated signaling and to determine the effects of altered CypA levels and activity on PRL signaling and breast cancer phenotype by combining biophysical structural investigations with studies in cell and animal models. The knowledge we obtained from this study will contribute to a greater understanding of the mechanism of PRL action. Our recent data suggest that CypA, serving as a molecular switch via its peptidyl-prolyl isomerase (PPI) activity, binds to and regulates the function of the PRLr through its X-box motif. From a translation perspective, we have also shown that the X-box peptide significantly blocks PRLr signaling. Given that the PRLr-triggered signals directly contribute to PRL-induced proliferation, survival, and motility of human breast cancer, the proposed study in detail on the effect of CypA on PRLr structure and function will have a significant impact on human breast cancer.