Novel Signaling Perturbation and Ribozyme Gene Therapy Procedure to Block Rho-Kinase (ROK) Activation and Breast Tumor Metastasis

摘要

In this study we have examined CD44 AN HYALURONAN (HA) receptor interaction with a RhoA-specific guanine nucleotide exchange factor (p11 5RhoGEF) in human metastatic breast tumor cells (MDA-MB-23 1 cell line). Immunoprecipitation and immunoblot analyses indicate that both CD44 and P115RhoGEF are expressed in MDA-MB-231 cells, and that these two proteins are physically associated as a complex in vivo. The binding of HA to MDA-MB-231 cells stimulates p115RhoGEF-mediated RhoA signaling and Rho-Kinase (ROK) activity which, in turn, increases serine/threonine phosphorylation of the adaptor protein, Gab-1 (Grb2-associated binder-1). Phosphorylated Gab-1 promotes PI3 kinase recruitment to CD44v3.