New, tacky oncogenes

The β and γ catenins both mediate cell-to-cell adhesion, with β catenin also being involved in a signal transduction cascade that promotes cell proliferation, but their role in tumorigenesis has been unclear. In the August 15 Genes & Development, Maralice Conacci-Sorrell and colleagues at The Weizmann Institute of Science, Rehovot, Israel, show that both β and γ catenins induce transcription of Nr-CAM (a neuronal cell adhesion molecule) and play a role in melanoma and colon cancer tumorigenesis, probably by promoting cell growth and motility (Genes Dev 2002, 16:2058-2072).

Conacci-Sorrell et al. used DNA microarrays to analyze human carcinoma cell lines and observed that expression of Nr-CAM was dramatically increased by β and γ catenin. Nr-CAM expression in mouse fibroblast cells caused rapid proliferation in cell culture, and when these cells were injected into nude mice they produced rapidly developing tumors. In addition Conacci-Sorrell et al., showed that Nr-CAM is highly expressed in murine and human melanoma cells and human colon cancer tissue, but not in normal colon tissue and melanocytes.

Because Nr-CAM is a molecule expressed on the outer surface of cells, the team suggest that new anti-cancer therapies based on Nr-CAM targeting could be more effective than those that focus on molecules expressed inside the cell.