title: Regulation of tumor progression via the Snail-RKIP signaling pathway by nicotine exposure in head and neck squamous cell carcinoma.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department and Graduate School of Pathology, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan.|Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Shin
authors.initials: S
authors.lastname: Nieh
authors.affiliation: Division of Colon and Rectal Surgery, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Shu-Wen
authors.initials: SW
authors.lastname: Jao
authors.affiliation: Department of Dentistry, Cheng Hsin Hospital, Taipei, Taiwan.
authors.forename: Chin-Yuh
authors.initials: CY
authors.lastname: Yang
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Kaohsiung Veterans General Hospital, Kaohsiung, Taiwan.|Department of Otolaryngology-Head and Neck Surgery, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Yaoh-Shiang
authors.initials: YS
authors.lastname: Lin
authors.affiliation: Department and Graduate School of Pathology, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Yi-Han
authors.initials: YH
authors.lastname: Tseng
authors.affiliation: Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan.
authors.forename: Chia-Lin
authors.initials: CL
authors.lastname: Liu
authors.affiliation: Division of Colon and Rectal Surgery, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan.|Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tsai-Yu
authors.initials: TY
authors.lastname: Lee
authors.affiliation: Institute of Environmental and Occupational Health Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Tsung-Yun
authors.initials: TY
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, National Defense Medical Center & Tri-Service General Hospital, Taipei, Taiwan.
authors.forename: Yueng-Hsiang
authors.initials: YH
authors.lastname: Chu
authors.affiliation: Department of Dental Hygiene, China Medical University, Taichung, Taiwan.
authors.forename: Su-Feng
authors.initials: SF
authors.lastname: Chen
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D017209:Apoptosis / Q000187:drug effects; D002273:Carcinogens / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000473:pathology*; D018929:Cell Culture Techniques / Q000379:methods; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D018450:Disease Progression; D019008:Drug Resistance, Neoplasm / Q000235:genetics; D058750:Epithelial-Mesenchymal Transition / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000473:pathology; D007527:Isoenzymes / Q000187:drug effects / Q000378:metabolism; D009062:Mouth Neoplasms / Q000473:pathology; D009361:Neoplasm Invasiveness / Q000235:genetics; D009367:Neoplasm Staging; D014411:Neoplastic Stem Cells / Q000187:drug effects; D009538:Nicotine / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000494:pharmacology*; D009602:Nitrosamines / Q000494:pharmacology*; D050697:Retinal Dehydrogenase / Q000187:drug effects / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071250:Snail Family Transcription Factors; D014062:Tongue Neoplasms / Q000473:pathology; D014157:Transcription Factors / Q000187:drug effects / Q000378:metabolism; D015854:Up-Regulation; D064569:alpha7 Nicotinic Acetylcholine Receptor / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: D002273:Carcinogens; D007527:Isoenzymes; D018722:Nicotinic Agonists; D009602:Nitrosamines; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D064569:alpha7 Nicotinic Acetylcholine Receptor; D009538:Nicotine; C016583:4-(N-methyl-N-nitrosamino)-1-(3-pyridyl)-1-butanone; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase
keywords: cancer stem cell (CSC) properties; epithelial-mesenchymal transition; head and neck squamous cell carcinoma (HNSCC); nicotine; tumor progression