Molecular alterations during colon tumorigenesis: An overview of growth regulatory pathways and potential therapeutic implications

RECENT ADVANCES in molecular genetics have identified alterations in specific dominantly acting proto-oncogenes and recessively acting tumor suppressor genes as important events in the development of human colorectal cancer. However, the molecular basis by which these changes induce the cascade of alterations in growth control and adhesion properties of tumor cells remains to be elucidated. To provide insight into these changes, an understanding is required of the role of specific signal transduction molecules in regulating proliferation and differentiation of normal colonic epithelial cells, as well as the alterations in these pathways that occur during tumorigenesis and tumor progression. This article reviews some of the important signaling molecules in colon cancer, including transforming growth factor-α and -β and the src family of tyrosine kinases. Also discussed is the role of the extracellular matrix in signaling.