HH/GLI signalling as a new therapeutic target for patients with oral squamous cell carcinoma

We found that GLI2, one of the main transcriptional activators of HH/GLI signalling, was expressed in 60 (44%) of the 136 OSCC samples and the expression was significantly associated with poor clinical outcomes. Only 44% of the patients whose tumours expressed GLI2 survived at 5 years after surgery compared to 77% of those whose tumours lacked the GLI2 expression (P < 0.0001). Both cyclopamine and GANT61 effectively inhibited GLI expression, slowed cell growth, promoted G1 arrest, increased apoptosis and inhibited migration of OSCC cells. Our results demonstrate that activation of HH/GLI pathway plays an important role in OSCC progression. Together with the finding that expression of GLI2 is strongly associated with a poor clinic outcome of OSCC patients, the data suggest that a subset of OSCC patients may benefit from anti-HH/GLI therapies.