NFATc2 in GalR2-mediated Head and Neck Cancer Tumor Progression

Galanin receptor 2 (GalR2) has mitogenic effects in neurons, but its role in invasion and migration in cancer is unknown. Our data show that GalR2 induces ERK activation and promotes tumor progression in HNSCC. NFATc2 is a transcription factor that is activated by ERK in melanoma and promotes PGE2 secretion in breast cancer. PGE2 and other cytokines have a crucial role in progression of HNSCC. Therefore, the hypothesis of this study is that NFATc2 mediates GalR2 induced secretion of PGE2 in HNSCC. Objectives: To determine if NFATc2 is expressed in HNSCC, if GalR2 induces cytokine secretion and if NFATc2 mediates GalR2-induced cytokine secretion in HNSCC. Methods: Expression of NFATc2 in HNSCC was evaluated by immunoblot analysis of HNSCC cell lysates and by immunohistochemical staining of tissue microarrays. Since NFATc2 is a transcription factor, nuclear translocation of NFATc2 was determined following galanin treatment in GalR2 transfected cells. PGE2 secretion was quantified by ELISA in cancer cell lines overexpressing GalR2 following siRNA-mediated knockdown of NFATc2. Results: NFATc2 is expressed in HNSCC tissue and cell lines. GalR2 promotes nuclear translocation of NFATc2 and induces secretion of PGE2 in HNSCC cells. siRNA-mediated knockdown of NFATc2 leads to decreased PGE2 secretion in HNSCC cells stably overexpressing GalR2. Conclusion: These data support that GalR2 induces NFATc2 translocaton and PGE2 secretion. Future studies will determine the role of NFATc2 in GALR2-mediated tumor progression. Knowledge of this signaling cascade may facilitate the development of targeted therapeutics. This study was supported in part by NIDCR F30DE021293, DE017977, DE019513, and the Tissue Engineering and Regeneration at Michigan (TEAM) training grant.