Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma

• Published in: Oncotarget Vol. 7; no. 23; pp. 33887 - 33900
• Main Authors: Kakuki, Takuya, Kurose, Makoto, Takano, Ken-Ichi, Kondoh, Atsushi, Obata, Kazufumi, Nomura, Kazuaki, Miyata, Ryo, Kaneko, Yakuto, Konno, Takumi, Takahashi, Syunta, Hatakeyama, Tsubasa, Kohno, Takayuki, Himi, Tetsuo, Kojima, Takashi
• Format: Journal Article
• Language: English
• Published: United States Impact Journals LLC 07-06-2016
• Subjects: beta Catenin - genetics; beta Catenin - metabolism; Biomarkers, Tumor - genetics; Biomarkers, Tumor - metabolism; Carcinoma, Squamous Cell - genetics; Carcinoma, Squamous Cell - metabolism; Carcinoma, Squamous Cell - pathology; Cell Adhesion Molecules - genetics; Cell Adhesion Molecules - metabolism; Cell Line, Tumor; Cell Movement; Cell Proliferation; GATA3 Transcription Factor - genetics; GATA3 Transcription Factor - metabolism; Gene Expression Regulation, Neoplastic; Head and Neck Neoplasms - genetics; Head and Neck Neoplasms - metabolism; Head and Neck Neoplasms - pathology; Humans; Neoplasm Invasiveness; NF-kappa B - metabolism; Receptors, Cell Surface - genetics; Receptors, Cell Surface - metabolism; Research Paper; RNA Interference; Signal Transduction; Squamous Cell Carcinoma of Head and Neck; Time Factors; Transcription Factors - genetics; Transcription Factors - metabolism; Transfection; Tumor Suppressor Proteins - genetics; Tumor Suppressor Proteins - metabolism; β-catenin; JAM-A; p63; GATA-3; head and neck squamous cell carcinoma
• ISSN: 1949-2553; 1949-2553
• DOI: 10.18632/oncotarget.8432

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.