[Frontiers in Bioscience 7, e1-8, January 1, 2002]

TARGETING ACTIN REMODELING PROFILES FOR THE DETECTION AND MANAGEMENT OF UROTHELIAL CANCERS - A PERSPECTIVE FOR BLADDER CANCER RESEARCH

JianYu Rao

Department of Pathology and Laboratory Medicine, University of California at Los Angeles Medical Center, Los Angeles, CA 90095

TABLE OF CONTENTS

1. Abstract
2.Introduction
3.The need for developing biomarkers for bladder cancer management
4. Actin and actin binding proteins

5. Regulation of actin assembly dynamics and actin signaling
6. Relationship of actin remodeling with transformation
7. Relationship of actin remodeling with apoptotic process
8. Actin remodeling pathways as novel targets for chemotherapeutic and chemopreventive drug developments

9. Summary and perspective
10. Acknowledgement
11. Reference

1. ABSTRACT

The actin cytoskeleton and numerous proteins associated with its regulation and function constitute over 25% of total proteins in the cell. Growing evidence from this laboratory and others shows that alterations of actin polymerization, or actin remodeling, plays a pivotal role in regulating the morphologic and phenotypic events of a malignant cell. The actin remodeling is the result of activation of oncogenic actin signaling pathways (e.g., Ras and Src), or inactivation of several important actin-binding proteins that have tumor suppressive functions (e.g., Gelsolin, E-Cadherin, etc.). Recently distinctive protein expression patterns of some of these genes in bladder cancer carcinogenic and progressive processes have been observed. Specific actin-pathway antagonists that have growth inhibitory effect on transformed cells, but not normal cells, have been developed. Our overall hypothesis is that actin alterations are progressive and that distinctive actin remodeling profiles are associated with different stages of cancer development and progression. These patterns can be used as markers for cancer early detection and prognostic indication. On the other hand, detection of specific types of actin-signaling pathway alterations also enables a targeted preventive or therapeutic intervention with specific actin signaling pathway blockers, thereby providing an actin-based paradigm for individualized monitoring and intervention of human bladder cancer.