Snail-induced epithelial-mesenchymal transition promotes cancer stem cell-like phenotype in head and neck cancer cells

• Published in: International journal of oncology Vol. 44; no. 3; pp. 693 - 699
• Main Authors: MASUI, TAKASHI, OTA, ICHIRO, YOOK, JONG-IN, MIKAMI, SHINJI, YANE, KATSUNARI, YAMANAKA, TOSHIAKI, HOSOI, HIROSHI
• Format: Journal Article
• Language: English
• Published: Greece D.A. Spandidos 01-03-2014; Spandidos Publications; Spandidos Publications UK Ltd
• Subjects: Cadherins - biosynthesis; cancer stem cell; Cancer therapies; Cell adhesion & migration; Cell Line, Tumor; Cisplatin - administration & dosage; Development and progression; epithelial-mesenchymal transition; Epithelial-Mesenchymal Transition - genetics; Gene Expression Regulation, Neoplastic - drug effects; Genetic aspects; Genotype & phenotype; Head & neck cancer; Head and neck cancer; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - pathology; Health aspects; Humans; Hyaluronan Receptors - biosynthesis; Isoenzymes - biosynthesis; Metastasis; Motility; Neoplastic Stem Cells - metabolism; Phenotype; Proteins; Retinal Dehydrogenase - biosynthesis; Snail; Snail Family Transcription Factors; Stem cells; Transcription factors; Transcription Factors - genetics; Tumors; United States > US
• ISSN: 1019-6439; 1791-2423
• DOI: 10.3892/ijo.2013.2225

Head and neck squamous cell carcinoma (HNSCC) is known to have a poor prognosis. The resistance to treatment and distant metastasis are important clinical problems in HNSCC. The epithelial-mesenchymal transition (EMT) is a key process in successful execution of many steps such as the invasion and metastasis for cancer cells. Snail is one of the master regulators that promote EMT in many types of malignancies including HNSCC. Recently, it has been shown that Snail-induced EMT could induce a cancer stem cell (CSC)-like phenotype in a number of tumor types. In this study, we investigated the role of Snail in inducing EMT properties and CSC-like phenotype in HNSCC. We established HNSCC cell lines transfected with Snail. E-cadherin was analyzed using western blot analysis and immunofluorescence staining. Cell migration and invasion were assessed using wound-healing assay and modified Boyden chamber assay, respectively. CSC markers of HNSCC, CD44 and aldehyde dehydrogenase 1 (ALDH1), were also evaluated with western blot analysis, and chemosensitivity was assessed with WST-8 assay. Introduction of Snail induced EMT properties in HNSCC cells and enhanced cell migration and invasion. Moreover, Snail-induced EMT gained CSC-like phenotype and was associated with increased chemoresistance. These results suggest that Snail could be one of the attractive targets for the development of therapeutic strategies in HNSCC.