The cell adhesion nectin-like molecules (Necl) 1 and 4 suppress the growth and tumorigenic ability of colon cancer cells.

A key step in human colon cancer development includes the hyperactivation of Wnt/beta-catenin signaling and the induction of beta-catenin-TCF target genes that participate in colon cancer progression. Recent studies identified members of the immunoglobulin-like cell adhesion molecules (IgCAM) of the L1CAM family (L1 and Nr-CAM) as targets of beta-catenin-TCF signaling in colon cancer cells. L1 was detected at the invasive front of colon cancer tissue and confers metastasis when overexpressed in cells. In contrast to L1, we did not detect in colon cancer cells significant levels of another IgCAM family of molecules, the nectin-like (Necl) receptors Necl1 and Necl4, while Necl4 was previously found in the normal small intestine and colon tissues. We studied the properties of colon cancer cells in which Necl4 and Necl1 were expressed either alone, or in combination, and found that such cells display a wide range of properties associated with tumor suppression. Expression of both Necl1 and Necl4 was the most efficient in suppressing the tumorigenicity of colon cancer cells. This was associated with enhanced rates of apoptosis and change in several apoptosis-related markers. In contrast to its capacity to suppress tumorigenesis, Necl4 was unable to affect the highly malignant and metastatic capacities of colon cancer cells in which L1 was overexpressed. Our results suggest that various IgCAM receptor families play different roles in affecting the tumorigenic function of the same cells, and that Necl1 and Necl4 can fulfill a tumor suppressive role.