Snail controls the mesenchymal phenotype and drives erlotinib resistance in oral epithelial and head and neck squamous cell carcinoma cells

Objective The presence of regional metastases in patients with head and neck squamous cell carcinoma (HNSCC) is a common and adverse event associated with poor prognosis. The authors' recent work on human HNSCC tissues underlies Snail's role as a molecular prognostic marker for HNSCC. Snail positivity is significantly predictive of poorly differentiated, lymphovascular invasive, and regionally metastatic tumors. Here, the authors investigate the capacity of Snail to drive epithelial-mesenchymal transition (EMT) in human oral epithelial cell lines and its ability to confer drug resistance. Study Design Snail was overexpressed in HNSCC and oral epithelial cell lines. Anchorage independent growth assays, wound healing assays, invasion and migration assays, spheroid modeling, and cell survival assays were performed. Setting Academic tertiary medical center. Subjects and Methods Snail overexpressing HNSCC (OSC, Tu212, Tu686) and oral epithelial cell lines (HOK 16-B, OKF-6) were evaluated using assays for wound healing, invasion and migration, 3-dimensional growth, Western blot, and immunofluorescence. Results The overexpression of Snail in human HNSCC and oral epithelial cell lines drives EMT. The transfection of Snail confers the expression of a mesenchymal molecular signature, including downregulation of the epithelial adherens, such as E-cadherin and β-catenin, and induction of mesenchymal markers. Snail-overexpressing cell lines demonstrate rapid growth in Anchorage-independent growth assays, a decreased capacity to form tight spheroids, an increased resistance to erlotinib, and an increased capacity for invasion. Conclusion Snail controls the mesenchymal phenotype and drives erlotinib resistance in HNSCC cells. Snail may prove to be a useful marker in predicting epidermal growth factor receptor inhibitor responsiveness.