The DCC Protein -- NEURAL DEVELOPMENT AND THE MALIGNANT PROCESS

Kimberly M. Rieger-Christ, Karina L. Brierley and Michael A. Reale

Department of Internal Medicine/Oncology, Yale School of Medicine/West Haven Veterans Administration Medical Center, 333 Cedar St., P.O. Box 208032, New Haven, CT 06520-8032

Received 8/25/97 Accepted 9/5/97

TABLE OF CONTENTS

1. Abstract

2. Introduction

3. DCC and Development

3.1. DCC guides axonal migrations

3.2 DCC guides cell migrations

3.3. Summary

4. DCC and Cancer

4.1. 18q Allelic loss and DCC expression studies

4.2. Experimental approaches

4.3. Summary

5. Perspective

6. Acknowledgments

7. References

1. ABSTRACT

The deleted in colorectal cancer (DCC) gene encodes a neural cell adhesion family molecule that was originally identified as a candidate tumor suppressor target of 18q allelic loss in colorectal cancer. However, the importance of the DCC protein has been most clearly demonstrated in neural development. Mutational and subsequent biochemical studies in C. elegans, Drosophila and vertebrates have shown that DCC functions in the guided migration of cells and cell processes in response to stimuli from netrins, a family of secreted laminin-like proteins. It appears that DCC may act in this signal transduction pathway as a netrin receptor or a component of the receptor complex, though a definitive receptor:ligand relationship has not yet been demonstrated. It is also clear that DCC can affect migrations in a netrin-independent manner, implying the existence of other DCC ligands. Though the loss of DCC expression appears to be a later event in several malignancies and is associated with disease dissemination, it has not been adequately demonstrated that DCC is the tumor suppressor gene targeted by 18q allelic loss. However, DCC expression does have potential clinical utility as it stratifies an important group of colorectal cancer patients into good and poor prognosis subgroups.