title: Anti-tumor effect of a novel FAK inhibitor TAE226 against human oral squamous cell carcinoma.
abstract: OBJECTIVE
  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 Tyr(397) inhibitor TAE226 and investigated its anti-tumor effects and mechanisms.
  
  
  METHODS
  Expression of phosphorylated FAK Tyr(397) 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 Tyr(397) and phospho AKT Ser(473), 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.
authors: Department of Oral and Maxillofacial Surgery, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama 700-8525, Japan.
authors: Naito
authors: N
authors: Kurio
authors: Tsuyoshi
authors: T
authors: Shimo
authors: Takuya
authors: T
authors: Fukazawa
authors: Tatsuo
authors: T
authors: Okui
authors: Nur Mohammad Monsur
authors: NM
authors: Hassan
authors: Tatsuki
authors: T
authors: Honami
authors: Yuu
authors: Y
authors: Horikiri
authors: Shinji
authors: S
authors: Hatakeyama
authors: Munenori
authors: M
authors: Takaoka
authors: Yoshio
authors: Y
authors: Naomoto
authors: Akira
authors: A
authors: Sasaki
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002294:Carcinoma, Squamous Cell / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002471:Cell Transformation, Neoplastic / Q000473:pathology; D005260:Female; D051416:Focal Adhesion Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009025:Morpholines / Q000494:pharmacology*; D009062:Mouth Neoplasms / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D051057:Proto-Oncogene Proteins c-akt / Q000037:antagonists & inhibitors
chemical_list: D009025:Morpholines; C524632:TAE226; D051416:Focal Adhesion Protein-Tyrosine Kinases; D051057:Proto-Oncogene Proteins c-akt