title: Overexpression of CRKII increases migration and invasive potential in oral squamous cell carcinoma.
abstract: CT10 regulator of kinase (CRK) was originally identified as an oncogene product of v-CRK in a CT10 chicken retrovirus system. Overexpression of CRKII has been reported in several human cancers. CRKII regulates cell migration, morphogenesis, invasion, phagocytosis, and survival; however, the underlying mechanisms are not well understood. In the present study, we evaluated the possibility of CRKII as an appropriate molecular target for cancer gene therapy. The expression of CRKII in 71 primary oral squamous cell carcinomas and 10 normal oral mucosal specimens was determined immunohistochemically, and the correlation of CRKII overexpression with clinicopathological factors was evaluated. Overexpression of CRKII was detected in 41 of 70 oral squamous cell carcinomas, the frequency being more significant than in normal oral mucosa. In addition, CRKII overexpression was more frequent in higher-grade cancers according to the T classification, N classification, and invasive pattern. Moreover, RNAi-mediated suppression of CRKII expression reduced the migration and invasion potential of an oral squamous cell carcinoma cell line, OSC20. Downregulation of CRKII expression also reduced the expression of Dock180, p130Cas, and Rac1, and the actin-associated scaffolding protein cortactin. These results indicate that the overexpression of CRKII is tightly associated with an aggressive phenotype of oral squamous cell carcinoma. Therefore, we propose that CRKII could be a potential molecular target of gene therapy by RNAi-targeting in oral squamous cell carcinoma.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Unit of Translational Medicine, Course of Medical and Dental Sciences, Nagasaki University Graduate School of Biomedical Sciences, Japan. shinshin@nagasaki-u.ac.jp
authors.forename: Shin-Ichi
authors.initials: S
authors.lastname: Yamada
authors.forename: Souichi
authors.initials: S
authors.lastname: Yanamoto
authors.forename: Goro
authors.initials: G
authors.lastname: Kawasaki
authors.forename: Satoshi
authors.initials: S
authors.lastname: Rokutanda
authors.forename: Hisanobu
authors.initials: H
authors.lastname: Yonezawa
authors.forename: Akiko
authors.initials: A
authors.lastname: Kawakita
authors.forename: Takayuki K
authors.initials: TK
authors.lastname: Nemoto
mesh_terms: D002294:Carcinoma, Squamous Cell / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement; D015971:Gene Expression Regulation, Enzymologic; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007150:Immunohistochemistry / Q000379:methods; D008954:Models, Biological; D009062:Mouth Neoplasms / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D050737:Proto-Oncogene Proteins c-crk / Q000096:biosynthesis*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D016896:Treatment Outcome
chemical_list: D050737:Proto-Oncogene Proteins c-crk