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Talin‐1 overexpression defines high risk for aggressive oral squamous cell carcinoma and promotes cancer metastasis
Author(s) -
Lai MingTsung,
Hua ChunHung,
Tsai MingHsui,
Wan Lei,
Lin YingJu,
Chen ChihMei,
Chiu IWen,
Chan Carmen,
Tsai FuuJen,
JinnChyuan Sheu Jim
Publication year - 2011
Publication title -
the journal of pathology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.964
H-Index - 184
eISSN - 1096-9896
pISSN - 0022-3417
DOI - 10.1002/path.2867
Subject(s) - metastasis , basal cell , cancer , cancer research , medicine , cancer metastasis , oncology , pathology
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 Sty 1 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. Copyright © 2011 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.