Objectives: To investigate whether NFATc2 mediates GalR2-induced proliferation and invasion in HNSCC.
Methods: Expression of NFATc2 in HNSCC was evaluated by immunoblot analysis of HNSCC cell lines and by immunohistochemical staining of HNSCC tissue. Nuclear translocation of NFATc2 was determined following galanin treatment in GalR2 transfected cells. Proliferation, invasion and PGE2 secretion were quantified in HNSCC cell lines overexpressing GalR2 with siNFATc2 or non target siRNA.
Results: NFATc2 is expressed in HNSCC. GalR2 promotes nuclear translocation of NFATc2 and induces secretion of PGE2 in HNSCC cells. In these cells, knockdown of NFATc2 inhibits PGE2 secretion, proliferation and invasion.
Conclusions: GalR2 induces PGE2 secretion and invasion in HNSCC via NFATc2. Since invasion is essential for tumor progression, the GalR2-NFATc2 signaling cascade may be an important therapeutic target.
This study was supported in part by NIDCR F30-DE021293-02, R01-DE018512, K02-DE019513, R21-DE017977, DE007057-32 (Tissue Engineering and Regeneration at Michigan training grant).
Keywords: Carcinogenesis, Invasion, Oral biology and Oral medicine