Cell Migration as a Therapeutic Target in Malignant Breast Cancer

摘要

The objects of this project are to develop a high-throughput method for screening potential inhibitors of breast cancer cell migration, and to apply this method to identify signaling events mediating constitutive migration of malignant breast cells. The pathways that control these signaling events may be targets for development of new classes of anti-tumor drugs. The significant advances made during this project include (1) development of an efficient, high- throughput migration assay compatible with drug screening; (2) identification of three molecules that are involved in integrin-mediated cell signaling and migration (RACK 1, Focal Adhesion Kinase, and Ca+2); (3) development of a model system for examining integrin-specific signaling in breast cells adhering to laminin-1; and (4) the identification of perillyl alcohol as a non-cytotoxic inhibitor of breast cell migration. The significance of this work is demonstration of the utility of the novel migration inhibitor drug screen we have developed, plus development of reagents that will enable us to examine the signaling associated with specific integrin complexes in breast cells.