Anti-tumor effect of a novel FAK inhibitor TAE226 against human oral squamous cell carcinoma

Summary Objectives Focal adhesion kinase (FAK) overexpression is frequently found in invasive and metastatic cancers, but its role in oral squamous cell carcinoma is not yet well understood. In order to seek therapies targeting oral squamous cell carcinoma, we developed the novel FAK Tyr397 inhibitor TAE226 and investigated its anti-tumor effects and mechanisms. Materials and Methods Expression of phosphorylated FAK Tyr397 was examined by immunohistochemical and immunoblot analysis. The effect of TAE226 on in vitro and in vivo studies were confirmed by proliferation, cell cycle, apoptosis and angiogenesis analysis. Results We found that phosphorylated FAK was highly expressed in human tongue oral squamous cell carcinoma in patients. Importantly, TAE226 greatly suppressed the proliferation, migration and invasion of human oral squamous cell carcinoma SAS cells with an apparent structural change of actin fiber and a loss of cell adhesion. In addition, TAE226 inhibited the expression of phospho-FAK Tyr397 and phospho AKT Ser473, resulting in caspase-mediated apoptosis. Furthermore, oral administration of TAE226 in mice suppressed the growth and angiogenesis of oral squamous cell carcinoma xenografts in vivo. Conclusions Our results provide compelling evidence that FAK is critically involved in oral squamous cell carcinoma and that the FAK inhibitor TAE226 can potentially be effectively used for the treatment of oral squamous cell carcinoma.