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

// Takuya Kakuki 1, 2 , Makoto Kurose 1 , Ken-ichi Takano 1 , Atsushi Kondoh 1 , Kazufumi Obata 1 , Kazuaki Nomura 1 , Ryo Miyata 1 , Yakuto Kaneko 1, 2 , Takumi Konno 2 , Syunta Takahashi 2 , Tsubasa Hatakeyama 2 , Takayuki Kohno 2 , Tetsuo Himi 1 , Takashi Kojima 2 1 Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan 2 Department of Cell Science, Research Institute for Frontier Medicine, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan Correspondence to: Takashi Kojima, email: ktakashi@sapmed.ac.jp Keywords: JAM-A, head and neck squamous cell carcinoma, β-catenin, p63, GATA-3 Received: December 05, 2015 Accepted: March 07, 2016 Published: March 28, 2016 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.