Snail controls the mesenchymal phenotype and drives erlotinib resistance in oral epithelial and head and neck squamous cell carcinoma cells - PubMed (original) (raw)

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

Miranda Dennis et al. Otolaryngol Head Neck Surg. 2012 Oct.

Erratum in

Abstract

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.

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Figures

Figure 1

Figure 1

Figure 1A: The generation of Snail over expressing HNSCC lines diminishes E-cadherin Figure 1B: The generation of Snail over expressing HNSCC lines diminishes E-cadherin

Figure 1

Figure 1

Figure 1A: The generation of Snail over expressing HNSCC lines diminishes E-cadherin Figure 1B: The generation of Snail over expressing HNSCC lines diminishes E-cadherin

Figure 2

Figure 2

A: Snail Overexpression drives EMT

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Figure 2

A: Snail Overexpression drives EMT

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Invasion and migration

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Figure 5

AIG assay

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Figure 6

Overexpresion of snail resistance to Tarceva

References

    1. Ferlay J, Bray F, Pisani P, Parkin DM. GLOBOCAN 2002 cancer incidence, mortality and prevalence worldwide IARC CancerBase No. 5, version 2.0. Lyon: IARC Press; 2004.
    1. National Cancer Institute Surveillance Epidemiology and End Results. http://seer.cancer.gov/
    1. Thiery JP, Acloque H, Huang RY, Nieto MA. Epithelial-mesenchymal transitions in development and disease. Cell. 2009 Nov 25;139(5):871–90. -PubMed
    1. St John MA, Dohadwala M, Luo J, Wang G, Lee G, Shih H, Heinrich E, Krysan K, Walser T, Hazra S, Zhu L, Lai C, Abemayor E, Fishbein M, Elashoff DA, Sharma S, Dubinett SM. Proinflammatory Mediators Upregulate Snail in Head and Neck Squamous Cell Carcinoma. Clin Cancer Res. 2009 Oct 1;15(19):6018–27. -PMC -PubMed
    1. Anderson SN, Towne DL, Burns DJ, Warrior U. A high-throughput soft agar assay for identification of anticancer compound. J Biomol Screen. 2007 Oct;12(7):938–45. -PubMed

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