title: Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma.
abstract: Junctional adhesion molecule-A (JAM-A), which belongs to the IgG superfamily, is a tight junction molecule associated with epithelial and endothelial barrier function. Overexpression of JAM-A is also closely associated with invasion and metastasis of cancers such as breast cancer, lung cancer and pancreatic cancer. However, little is known about the mechanism in overexpression of JAM-A in head and neck squamous cell carcinoma (HNSCC). In the present study, we found high expression of JAM-A at the protein and mRNA levels in HNSCC tissues, including those of the oropharynx, larynx, and hypopharynx, together with high protein expression of β-catenin, p63, ΔNp63 and GATA-3. Furthermore, in ELISA, a significant increase of soluble JAM-A in the sera of HNSCC patients was observed compared to healthy subjects. Knockdown of JAM-A by siRNA inhibited cell proliferation, invasion and migration in the HNSCC cell line Detroit562 in vitro. JAM-A expression in Detroit562 was increased via a distinct signal transduction pathway including NF-κB. Expression of JAM-A, β-catenin, p63 and ΔNp63 in Detroit562 was decreased under hypoxia. Knockdown of p63, ΔNp63 or GATA-3 by siRNAs reduced JAM-A expression in Detroit562. In primary cultured HNSCC cells in which CK7, p63, ΔNp63 and GATA-3 were detected, JAM-A expression was decreased by knockdown of p63 or ΔNp63. These results indicate that JAM-A is a biomarker of malignancy in HNSCC and that plasma soluble JAM-A may contribute to serum-based diagnosis of HNSCC. The mechanism of dysregulation of JAM-A via p63/GATA-3 is important in possible molecular targeted therapy for HNSCC.
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.|Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Takuya
authors.initials: T
authors.lastname: Kakuki
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Kurose
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Takano
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kondoh
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Kazufumi
authors.initials: K
authors.lastname: Obata
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Kazuaki
authors.initials: K
authors.lastname: Nomura
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Ryo
authors.initials: R
authors.lastname: Miyata
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.|Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Yakuto
authors.initials: Y
authors.lastname: Kaneko
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Takumi
authors.initials: T
authors.lastname: Konno
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Syunta
authors.initials: S
authors.lastname: Takahashi
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Tsubasa
authors.initials: T
authors.lastname: Hatakeyama
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Kohno
authors.affiliation: Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Tetsuo
authors.initials: T
authors.lastname: Himi
authors.affiliation: Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Kojima
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics / Q000378:metabolism*; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002465:Cell Movement; D049109:Cell Proliferation; D050990:GATA3 Transcription Factor / Q000235:genetics / Q000378:metabolism*; D015972:Gene Expression Regulation, Neoplastic; D006258:Head and Neck Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016328:NF-kappa B / Q000378:metabolism; D009361:Neoplasm Invasiveness; D034622:RNA Interference; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000077195:Squamous Cell Carcinoma of Head and Neck; D013997:Time Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; D015815:Cell Adhesion Molecules; C407243:F11R protein, human; D050990:GATA3 Transcription Factor; C494749:GATA3 protein, human; D016328:NF-kappa B; D011956:Receptors, Cell Surface; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D051176:beta Catenin
keywords: GATA-3; JAM-A; head and neck squamous cell carcinoma; p63; β-catenin