title: Talin-1 overexpression defines high risk for aggressive oral squamous cell carcinoma and promotes cancer metastasis.
abstract: Oral squamous cell carcinoma (OSCC) is highly invasive and is associated with frequent tumour recurrences and lymph node metastases. Identification of genes involved in the aggressiveness of OSCC may provide new targets for clinical intervention. A genome-wide study based on the Sty1 250K SNP array indicated the involvement of the Talin-1 (TLN1) gene in the 9p13.3 amplicon, which was further validated by dual colour fluorescence in situ hybridization (FISH). Comparative analyses revealed that TLN1 was the most highly expressed integrin-cytoskeleton cross-linker that can trigger integrin activation. IHC analyses and mouse study also revealed an association between TLN1 overexpression and advanced OSCC with invasion to adjacent tissues. Survival analyses indicated a significant association between TLN1 genetic gain/overexpression and a reduced overall survival in patients. Functional knockdown by a dominant negative TLN1 fragment reduced cell growth and invasiveness in TLN1-overexpressing cells via inactivation of downstream oncogenic signalling. The present study suggests an important role for TLN1 in oral cancer development. TLN1 overexpression could serve as a diagnostic marker for aggressive phenotypes and a potential target for treating OSCC.
authors.affiliation: Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan.
authors.forename: Ming-Tsung
authors.initials: MT
authors.lastname: Lai
authors.forename: Chun-Hung
authors.initials: CH
authors.lastname: Hua
authors.forename: Ming-Hsui
authors.initials: MH
authors.lastname: Tsai
authors.forename: Lei
authors.initials: L
authors.lastname: Wan
authors.forename: Ying-Ju
authors.initials: YJ
authors.lastname: Lin
authors.forename: Chih-Mei
authors.initials: CM
authors.lastname: Chen
authors.forename: I-Wen
authors.initials: IW
authors.lastname: Chiu
authors.forename: Carmen
authors.initials: C
authors.lastname: Chan
authors.forename: Fuu-Jen
authors.initials: FJ
authors.lastname: Tsai
authors.forename: Jim
authors.initials: J
authors.lastname: Jinn-Chyuan Sheu
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D014408:Biomarkers, Tumor / Q000096:biosynthesis* / Q000235:genetics; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D002455:Cell Division / Q000502:physiology; D002471:Cell Transformation, Neoplastic / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D055785:Gene Knockdown Techniques; D006801:Humans; D008297:Male; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016019:Survival Analysis; D016608:Talin / Q000096:biosynthesis* / Q000235:genetics; D014407:Tumor Cells, Cultured
chemical_list: D014408:Biomarkers, Tumor; D009363:Neoplasm Proteins; C518832:TLN1 protein, human; D016608:Talin