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Regulation of tumor progression via the Snail‐RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma
Author(s) -
Nieh Shin,
Jao ShuWen,
Yang ChinYuh,
Lin YaohShiang,
Tseng YiHan,
Liu ChiaLin,
Lee TsaiYu,
Liu TsungYun,
Chu YuengHsiang,
Chen SuFeng
Publication year - 2015
Publication title -
head and neck
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.012
H-Index - 127
eISSN - 1097-0347
pISSN - 1043-3074
DOI - 10.1002/hed.23820
Subject(s) - cancer research , head and neck squamous cell carcinoma , homeobox protein nanog , snail , metastasis , cancer , signal transduction , cancer stem cell , biology , chemistry , medicine , microbiology and biotechnology , head and neck cancer , gene , induced pluripotent stem cell , ecology , embryonic stem cell , biochemistry
Background Recent studies suggest that long‐term exposure of the carcinogen 4‐methylnitrosamino‐1–3‐pyridyl‐1‐butanone (NNK) found in tobacco smoke is involved in the progression of head and neck squamous cell carcinoma (HNSCC). The underlying nicotine‐mediated mechanism remains unclear. Methods An analysis of SCC‐25 and Fadu cells with or without NNK exposure focusing on the evaluation of migration and invasion abilities, the expression of epithelial–mesenchymal transition, drug‐resistance‐related genes, properties of cancer stem cells (CSCs), and anti‐apoptosis was performed. Results Long‐term NNK exposure enhances migration and invasion with morphological alterations in a dose‐dependently manner. Furthermore, NNK exposure also upregulates Snail, promotes sphere‐forming ability, and overexpresses aldehyde dehydrogenase 1 (ALDH1), Nanog, OCT4, ABCG2, and MDR1. Conclusion The current study confirmed that long‐term NNK exposure plays a role in HNSCC by increasing anti‐apoptosis and therapeutic resistance via the Snail‐RKIP signaling pathway. Our data also suggest that α7 nicotinic acetylcholine receptor (α7‐nAChR) inhibition or targeting Snail may provide a feasible rationale for preventing the progression of HNSCC. © 2015 Wiley Periodicals, Inc. Head Neck 37: 1712–1721, 2015