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

摘要

Aberrant activation of HH/CLI has recently been reported in multiple cancer types, yet its role in oral squamous cell carcinoma (OSCC) has not been investigated. In this study, we aimed to determine the role of HH/CLl in OSCC. Expression of GLl11 and CL12 was examined in OSCC samples from 136 patients by immunohistochem-istry and correlated with clinicopathology parameters and clinical outcomes of the patients. Two HH/CL1 specific small molecule inhibitors cyclopamine and CANT61, were used to test the potential role of HH/ CLl in OSCC. We found that GLI2, one of the main transcriptional activators of HH/GLl 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 CL12 survived at 5 years after surgery compared to 77% of those whose tumours lacked the CLI2 expression (P< 0.0001). Both cyclopamine and GANT61 effectively inhibited GLl 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 antiHH/GLl therapies.