Talin-1 overexpression defines high risk for aggressive oral squamous cell carcinoma and promotes cancer metastasis

Ming Tsung Lai, Chun Hung Hua, Ming Hsui Tsai, Lei Wan, Ying Ju Lin, Chih Mei Chen, I. Wen Chiu, Carmen Chan, Fuu Jen Tsai, Jinn Chyuan Jim Sheu

Research output: Contribution to journalJournal Article peer-review

68 Scopus citations

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.

Original languageEnglish
Pages (from-to)367-376
Number of pages10
JournalJournal of Pathology
Volume224
Issue number3
DOIs
StatePublished - 07 2011
Externally publishedYes

Keywords

  • 9p13.3 amplicon
  • Talin-1 (TLN1)
  • invasion
  • oral squamous cell carcinoma (OSCC)

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