Recurrent gain on chromosome 3q26 encompassing the gene locus for the
transcription factor SOX2 is a frequent event in human
squamous cell carcinoma, including
head and neck squamous cell carcinoma (
HNSCC). Numerous studies demonstrated that SOX2 expression and function is related to distinct aspects of
tumor cell pathophysiology. However, the underlying molecular mechanisms are not well understood, and the correlation between SOX2 expression and clinical outcome revealed conflicting data. Transcriptional profiling after silencing of SOX2 expression in a
HNSCC cell line identified a set of up-regulated genes related to cell motility (e.g. VIM, FN1, CDH2). The inverse regulation of SOX2 and aforementioned genes was validated in 18 independent
HNSCC cell lines from different anatomical sites. The inhibition of cell migration and invasion by SOX2 was confirmed by constant or conditional gene silencing and accelerated motility of
HNSCC cells after SOX2 silencing was partially reverted by down-regulation of
vimentin. In a retrospective study, SOX2 expression was determined by immunohistochemical staining on tissue microarrays containing primary
tumor specimens of two independent
HNSCC patient cohorts. Low SOX2 expression was found in 19.3% and 44.9% of primary
tumor specimens, respectively. Univariate analysis demonstrated a statistically significant correlation between low SOX2
protein levels and reduced progression-free survival (Cohort I 51 vs. 16 months; Cohort II 33 vs. 12 months) and overall survival (Cohort I 150 vs. 37 months; Cohort II 33 vs. 16 months). Multivariate Cox proportional hazard model analysis confirmed that low SOX2 expression serves as an independent prognostic marker for
HNSCC patients. We conclude that SOX2 inhibits
tumor cell motility in
HNSCC cells and that low SOX2 expression serves as a prognosticator to identify
HNSCC patients at high risk for treatment failure.