Caveolin-1, a novel Id1 binding partner, and its role on Id1-induced behavioral change in prostate cancer cells

Abstract

Id-1 (Inhibitor of Differentiation/DNA binding-1) is reported to promote cell proliferation, invasion and survival in many types of human cancer cells through multiple signaling pathways. In this study, we identified a novel Id-1 interacting protein, caveolin-1 (Cav-1), a cell membrane protein and a positive regulator of cell survival and metastasis in prostate cancer. Using immunoprecipitation method, we found that the helix-loop-helix domain of the Id-1 protein was essential for the physical interaction between Id-1 and Cav-1. We also demonstrated in prostate cancer cells that the physical interaction between Id-1 and Cav-1 played a key role in the Id-1-induced epithelial-mesenchymal transition and cell migration as well as resistance to taxol-induced apoptosis. Our results also revealed that the Id-1-induced Akt activation through promoting the binding activity between Cav-1 and PP2A phosphatase was responsible for the synergistic effect between these two proteins. Our study demonstrates a novel Id-1 binding partner and suggests a molecular mechanism that mediates the function of Id-1 in promoting prostate cancer cell invasion and survival through activation of the Akt pathway [(HKU7478/03M) to XHW and YCW (HKU7490.03M, 7470/04M, NSFC/RGC N_HKU738/03, HKU Foundation Seed Fund, 03)].