Transcriptional profiling identifies upregulated genes following induction of epithelial-mesenchymal transition in squamous carcinoma cells

During the progression of head and neck squamous cell carcinoma (HNSCC), the induction of an epithelial–mesenchymal transition (EMT) program may play a critical role in the dissemination of cells from the primary tumor to distant metastatic foci. The process of EMT involves the activation of several important genes and pathways to help maintain survival and growth and evolve into highly invasive and metastatic variants. In this study, expression microarray analysis identified a set of 145 upregulated genes in EMT-like HNSCC cells. Some of the strongly upregulated transcripts include genes that are reportedly involved in invasion and metastasis, such as DOCK10, LOX, ROBO1 and SRGN. Importantly, the Tbx3 gene, a member of the T-box transcription factor, was strongly upregulated in SCC cells displaying an EMT-like phenotype compared to cells with an epitheloid, non-EMT behavior. Tbx3 was also found to be strongly upregulated at the protein and gene expression level in an experimental model of snail-induced EMT cells. In addition, siRNA-induced Tbx3 depletion modestly suppressed cell invasion while enhancing Tbx3-mediated resistance to anoikis. Our findings provide evidence that Tbx3 overexpression promotes SCC cell survival displaying an EMT phenotype. This set of newly identified genes that are modulated during EMT-like conversion may be important diagnostic biomarkers during the process of HNSCC progression.

► Identified a set of 145 upregulated genes in EMT-like HNSCC.
► Tbx3 gene is strongly upregulated in HNSCC cells with EMT-like phenotype.
► Snail regulates Tbx3 at gene expression level.
► Knockdown of Tbx3 in EMT-like SCC cell line suppressed resistance to anoikis.