Snail-induced EMT promotes cancer stem cell-like properties in head and neck cancer cells.
Epithelial-mesenchymal transition (EMT) is a key process involved in the invasion and metastasis of cancer cells. Furthermore, EMT can induce a cancer stem cell (CSC)-like phenotype in a number of tumor types. We demonstrated that Snail is one of the master regulators that promotes EMT and mediates cancer cell migration and invasion in many types of malignancies including head and neck squamous cell carcinoma (HNSCC). In the present study, we investigated the role of Snail in inducing and maintaining CSC-like properties through EMT in HNSCC. We established HNSCC cell lines transfected with Snail. Stem cell markers were evaluated with real-time RT-PCR and western blot analysis. CSC properties were assessed using sphere formation and WST-8 assays as well as chemosensitivity and chick chorioallantoic membrane in vivo invasion assays. Introduction of Snail induced EMT properties in HNSCC cells. Moreover, Snail-induced EMT maintained the CSC-like phenotype, and enhanced sphere formation capability, chemoresistance and invasive ability. These data suggest that Snail could be one of the critical molecular targets for the development of therapeutic strategies for HNSCC.
Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Ichiro
I
Ota
Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Takashi
T
Masui
Department of Molecular Pathology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Miyako
M
Kurihara
Department of Oral Pathology, Oral Cancer Research Institute, College of Dentistry, Yonsei University, Seoul 120-752, Republic of Korea.
Jong-In
JI
Yook
Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Shinji
S
Mikami
Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Takahiro
T
Kimura
Department of Pathology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Keiji
K
Shimada
Department of Pathology, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Noboru
N
Konishi
Department of Otolaryngology, Kinki University School of Medicine, Nara Hospital, Ikoma, Nara 630-0293, Japan.
Katsunari
K
Yane
Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Toshiaki
T
Yamanaka
Department of Otolaryngology-Head and Neck Surgery, Nara Medical University, Kashihara, Nara 634-8522, Japan.
Tadashi
T
Kitahara
D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D058750:Epithelial-Mesenchymal Transition; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D014411:Neoplastic Stem Cells / Q000378:metabolism / Q000473:pathology*; D000071250:Snail Family Transcription Factors; D000077195:Squamous Cell Carcinoma of Head and Neck; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; D002945:Cisplatin