Auxiliary diagnosis and molecular targeted therapy by tight junction related molecule JAM-A in head and neck cancer

• Project/Area Number: 15K10817
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Sapporo Medical University
• Principal Investigator: MAKOTO KUROSE 札幌医科大学, 医学部, 講師 (60404696)
• Co-Investigator(Kenkyū-buntansha): 高野 賢一 札幌医科大学, 医学部, 准教授 (70404689)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2017: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2016: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
• Keywords: Head and neck cancer / squamous cell carcinomas / JAM-A / p63/GATA-3 / HDAC / malignancy / 頭頸部扁平上皮癌 / 悪性化 / シグナル伝達経路 / HDAC阻害剤 / NF-ｋBシグナル

Outline of Final Research Achievements

In the present study, we investigated the possibility about auxiliary diagnosis and targeted therapy of squamous cell carcinomas in head and neck cancer by tight junction related molecule JAM-A. We found high expression of JAM-A at the protein and mRNA levels in head and neck squamous cell carcinoma (HNSCC) tissue. Soluble JAM-A in serum of HNSCC patients was high level compared to the normal. Overexpression of JAM-A in HNSCC cell line Detroit562 was in part regulated via p63/GATA-3. We used inhibitors of histone deacetylase (HDAC). By using HNSCC cell line Detroit562, treatment with a panHDAC inhibitor tricostatin A (TSA) or specific inhibitors of HDAC1 and HDAC6 prevented the invasion, migration and proliferation of cancer cells in vitro. Furthermore, they also inhibited expression of p63 and JAM-A in Detroit562 cells. Taken together, inhibitors of HDAC are available in possible about auxiliary diagnosis and molecular targeted therapy for HNSCC via p63/JAM-A.

Research Products

• [Journal Article] Regulation of claudin-4 via p63 in human epithelial cells. (2017)
  • Author(s): Kojima T, Kohno T, Kubo T, Kaneko Y, Kakuki T, Kakiuchi A, Kurose M, Takano KI, Ogasawara N, Obata K, Nomura K, Miyata R, Konno T, Ichimiya S, Himi T.
  • Journal Title: Ann N Y Acad Sci. Volume: 1405 Issue: 1 Pages: 25-31
  • DOI: 10.1111/nyas.13456
  • Peer Reviewed / Open Access
• [Journal Article] The behavior and role of lipolysis-stimulated lipoprotein receptor, a component of tricellular tight junctions, in head and neck squamous cell carcinomas. (2016)
  • Author(s): Takano K, Kakuki T, Obata K, Nomura K, Miyata R, Kondo A, Kurose M, Kakiuch A, Kaneko Y, Kohno T, Himi T, Kojima T.
  • Journal Title: Anticancer Research Volume: 36 Pages: 5895-5904
• [Journal Article] Junctional Adhesion Molecule-A in Head and Neck Squamous Cell Carcinoma. (2016)
  • Author(s): Kurose M, Kakuki T, Takano K, Kondo A, Obata K, Nomura K, Miyata R, Kaneko Y, Konno T, Kohno T, Kojima T, Himi T.
  • Journal Title: Adv. Otorhinolaryngol Volume: 77 Pages: 92-97
• [Journal Article] Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma. (2016)
  • Author(s): Kakuki T, Kurose M, TakanoK, Kondoh A, Obata K, Nomura K, Miyata R, Kaneko Y, Konno T, Takahashi S, Hatakeyama T, Kohno T, Himi T, Kojima
  • Journal Title: Oncotarget Volume: 7 Pages: 33887-33900
• [Journal Article] Dysregulation of junctional adhesion molecule-A via p63/GATA-3 in head and neck squamous cell carcinoma. (2016)
  • Author(s): Kakuki T, Kurose M, TakanoK, Kondoh A, Obata K, Nomura K, Miyata R, Kaneko Y, Konno T, Takahashi S, Hatakeyama T, Kohno T, Himi T, Kojima T.
  • Journal Title: Oncotarget Volume: . Issue: 23 Pages: 1-14
  • DOI: 10.18632/oncotarget.8432
  • Peer Reviewed / Open Access
• [Presentation] The behavior and role of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in head and neck squamous cell carcinomas (2017)
  • Author(s): Makoto Kurose, Akito Kakiuchi, Kenichi Takano, Atsushi Kondo, Takuya Kakuki, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Yakuto Kaneko, Tetsuo Himi and Takashi Kojima
  • Organizer: 第5回アジア頭頚部癌学会
  • Place of Presentation: インドネシア、バリ
  • Year and Date: 2017-03-23
  • Int'l Joint Research
• [Presentation] Effects of histone deacetylase inhibitors on malignancy via p63/JAM-A in head and neck cancer (2017)
  • Author(s): Akito Kakiuchi, Takuya Kakuki, Makoto Kurose, Kenichi Takano, Atsushi Kondo, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Yakuto Kaneko, Tetsuo Himi and Takashi Kojima
  • Organizer: 第5回アジア頭頚部癌学会
  • Place of Presentation: インドネシア、バリ
  • Year and Date: 2017-03-23
  • Int'l Joint Research
• [Presentation] The behavior and role of tricellular tight junction protein lipolysis-stimulated lipoprotein receptor in head and neck squamous cell carcinomas. (2017)
  • Author(s): Makoto Kurose, Akito Kakiuchi, Kenichi Takano, Atsushi Kondo, Takuya Kakuki, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Yakuto Kaneko, Tetsuo Himi, Takashi Kojima．
  • Organizer: 5th Congress of Asian Society for Head and Neck Oncology
  • Int'l Joint Research
• [Presentation] Effects of histone deacetylase (HDAC) inhibitors on malignancy via p63/JAM-A in head and neck cancer. (2017)
  • Author(s): Akito Kakiuchi, Takuya Kakuki, Makoto Kurose, Kenichi Takano, Atsushi Kondo, Kazufumi Obata, Kazuaki Nomura, Ryo Miyata, Yakuto Kaneko, Tetsuo Himi and Takashi Kojima.
  • Organizer: 5th Congress of Asian Society for Head and Neck Oncology
  • Int'l Joint Research
• [Presentation] 頭頸部扁平上皮癌におけるヒストン脱アセチル化酵素(HDAC)阻害剤のp63依存性タイト結合分子を介した抗腫瘍効果 (2017)
  • Author(s): 垣内晃人、角木拓也、黒瀬誠、高野賢一、近藤敦、小幡和史、野村一顕、宮田亮、金子躍人、幸野貴之、氷見徹夫、小島隆
  • Organizer: 第68回日本細胞生物学会
• [Presentation] ヒストン脱アセチル化酵素(HDAC)阻害による頭頸部扁平上皮癌タイト結合分子の変化と抗腫瘍効果 (2017)
  • Author(s): 垣内晃人、角木拓也、黒瀬誠、高野賢一、近藤敦、小幡和史、野村一顕、宮田遼、金子躍人、氷見徹夫、小島隆
  • Organizer: 2017年生命科学系学会合同年次大会
• [Presentation] 頭頸部扁平上皮癌におけるp63/GATA-3経路を介したタイト結合分子JAM-Aの発現調節機構 (2015)
  • Author(s): 角木拓也、黒瀬誠、高野賢一、近藤敦、小幡和史、野村一顕、宮田遼、金野匠、高橋俊太、畠山翔翼、幸野貴幸、氷見徹夫、小島隆
  • Organizer: 第６７回日本細胞生物学会
  • Place of Presentation: タワーホール船橋（東京都江戸川区）
  • Year and Date: 2015-06-30
• [Presentation] The Serum Solubilization JAM-A Level of the Head and Neck Squamous Cell Carcinoma Patient Rises. (2015)
  • Author(s): Makoto Kurose, et al.
  • Organizer: 第39回日本頭頸部がん学会総会, 第４回アジア頭頸部癌学会
  • Place of Presentation: 神戸国際会議場（神戸市）
  • Year and Date: 2015-06-03
  • Int'l Joint Research