title: Snail-induced epithelial-mesenchymal transition promotes cancer stem cell-like phenotype in head and neck cancer cells.
abstract: 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.
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Masui
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
authors.forename: Ichiro
authors.initials: I
authors.lastname: Ota
authors.affiliation: Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul 120-752, Republic of Korea.
authors.forename: Jong-In
authors.initials: JI
authors.lastname: Yook
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Mikami
authors.affiliation: Department of Otolaryngology, Kinki University School of Medicine, Nara Hospital, Ikoma, Nara 630-0293, Japan.
authors.forename: Katsunari
authors.initials: K
authors.lastname: Yane
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Yamanaka
authors.affiliation: Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Hosoi
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D015820:Cadherins / Q000096:biosynthesis; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000008:administration & dosage; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000235:genetics* / Q000473:pathology; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007527:Isoenzymes / Q000096:biosynthesis; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D050697:Retinal Dehydrogenase / Q000096:biosynthesis; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics*
chemical_list: D015820:Cadherins; D018960:Hyaluronan Receptors; D007527:Isoenzymes; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase; D002945:Cisplatin