Oncotarget

Research Papers:

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

Takuya Kakuki, Makoto Kurose, Ken-ichi Takano, Atsushi Kondoh, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Yakuto Kaneko, Takumi Konno, Syunta Takahashi, Tsubasa Hatakeyama, Takayuki Kohno, Tetsuo Himi and Takashi Kojima _

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Oncotarget. 2016; 7:33887-33900. https://doi.org/10.18632/oncotarget.8432

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Abstract

Takuya Kakuki1,2, Makoto Kurose1, Ken-ichi Takano1, Atsushi Kondoh1, Kazufumi Obata1, Kazuaki Nomura1, Ryo Miyata1, Yakuto Kaneko1,2, Takumi Konno2, Syunta Takahashi2, Tsubasa Hatakeyama2, Takayuki Kohno2, Tetsuo Himi1, Takashi Kojima2

1Department of Otolaryngology, Sapporo Medical University School of Medicine, Sapporo 060-8556, Japan

2Department 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.


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