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.

Contributions of talin-1 to glioma cell–matrix tensional homeostasis

“…Our findings also contrast somewhat with previous observations with embryonic stem-cell-derived fibroblasts, in which talin-1 suppression was found not to affect spreading [26]. The reduced motility observed in talin-1-deficient glioma cells is consistent with previous observations with prostate cancer and oral squamous carcinoma cells [17,18]. Cell motility involves polymerization of actin at the leading edge, stabilization of leading edge by formation of cell -ECM adhesions and myosin-dependent retraction of the trailing edge through disassembly of adhesions [38].…”

“…While focal adhesions are complex and dynamic structures with more than 80 known molecular components [16], the protein talin (specifically, its two human isoforms, talin-1 and talin-2) has garnered specific interest because of its abnormal regulation in several tumour types. For example, in oral squamous cell carcinoma, talin-1 overexpression has been correlated with a metastatic phenotype [17]. Similarly, in prostate cancer cells, talin-1 overexpression contributes to enhanced adhesion, migration and invasion through activation of survival signals and rendering resistance to anoikis [18].…”

Phosphatidylinositol Phosphate 5-Kinase Iγi2 in Association with Src Controls Anchorage-independent Growth of Tumor Cells

“…Conversely, talin interaction with actin is regulated by phosphatidylinositol 4,5-biphosphate (46), suggesting their integrative and collaborative function. As talin is emerging as a potential regulator of oncogenesis, Src regulation of PIPKI␥i2 interaction with talin is fully consistent with a collaborative role in anchorage-independent growth (5,47,48).…”

Talin-1 Correlates with Reduced Invasion and Migration in Human Hepatocellular Carcinoma Cells

“…The overexpression of Talin-1 has been reported to enhance prostate cancer cell adhesion, migration, and invasion by activating survival signals and conferring resistance to anoikis (Sakamoto et al, 2010). TLN1 overexpression could serve as a diagnostic marker for aggressive phenotypes and a potential target for treating OSCC (Lai et al, 2011). The expression of KIF14 and TLN 1 is a prognostic marker for a better outcome after cytotoxic chemotherapy, and the inhibition of these genes can sensitize KIF14-and TLN1-overexpressing TNBC cells to therapeutic intervention (Singel et al, 2013).…”