Expression of human UNC5 in head and neck squamous cell carcinoma

Proc Amer Assoc Cancer Res, Volume 47, 2006 4480 Head and neck squamous cell carcinoma (HNSCC) is the sixth most common cancer worldwide. Recent studies have shown that DCC (Deleted in Colorectal Cancer) and UNC5 family members (UNC5A, UNC5B, UNC5C, and UNC5D in human) act as dependence receptors of Netrin-1, which induce apoptosis when unbound to their ligands. Binding of Netrin-1 to its receptors DCC and UNC5 activate p53 pathways that either upregulates (induction) or downregulates (suppression) apoptosis. The potential suppressor function of the Netrin pathway in tumorigenesis prompted us to study the expression of human UNC5 orthologues involved in the apoptosis pathway. Various cell lines (normal human oral keratinocytes OKF6 TERT1 and head and neck cancer cell lines JHU011, JHU012, JHU013, and JHU019) and two normal and eight HNSCC tissues were studied. UNC5A, UNC5B, and UNC5C were downregulated (75%, 75%, and 50% respectively) in tumor samples. These results suggest that the signaling functions of the netrin/DCC/UNC5 pathway is disrupted in HNSCC. UNC5A, UNC5B, and UNC5C receptors may represent tumor suppressor genes whose protein products inhibit tumorigenesis by inducing apoptosis.