Abstract
Objective: Snail positivity is predictive of poorly differentiated, invasive, and regionally metastatic HNSCC tumors. We have demonstrated the role of Snail in the inflammation-induced promotion of EMT. Here, we investigate the capacity of Snail to drive EMT in human oral epithelial cell lines, and its ability to confer drug resistance. Method: Snail was overexpressed in HOK and OKF oral epithelial cell lines. AIG assays, wound healing assays, invasion and migration assays, spheroid modeling, and drug resistance assays were performed. Differential gene expression between Snail-overexpressing and control epithelial and tumor cell lines was evaluated using gene expression microarray analysis. Results: The overexpression of Snail in human oral epithelial cell lines (HOK, OKF) drives EMT. OKF-Snail and HOK-Snail lines demonstrate growth in anchorage-independent growth assays; a decreased capacity to form tight spheroids; increased resistance to erlotinib; and a highly invasive and migratory nature. Gene expression analysis also revealed Snail-associated differential gene expression with the potential to affect inflammatory cytokine regulation, migration, invasion, and diverse aspects of HNSCC progression. Conclusion: Snail controls the mesenchymal phenotype and drives erlotinib resistance in HNSCC cells. Snail may prove to be a useful marker in predicting EGFR inhibitor responsiveness.
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