The role of AP-1 mediated miRNA on reginonal metastatic process of head and neck canceer

• Project/Area Number: 16K11240
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Otorhinolaryngology
• Research Institution: Yokohama City University
• Principal Investigator: Daisuke Sano 横浜市立大学, 医学部, 講師 (10620990)
• Co-Investigator(Kenkyū-buntansha): 折舘 伸彦 横浜市立大学, 医学研究科, 教授 (90312355)
• Research Collaborator: TAKAHASHI Hideaki
• Project Period (FY): 2016-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,680,000 (Direct Cost: ¥3,600,000、Indirect Cost: ¥1,080,000); Fiscal Year 2018: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2017: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2016: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
• Keywords: 頭頸部癌扁平上皮癌 / 頸部リンパ節転移 / AP-1 / FosL1 / 頭頸部癌 / AP-1遺伝子群 / FOSL1 / microRNA / エクソソーム 由来 miRNA

Outline of Final Research Achievements

We initially performed the upstream and key nodes analysis related with whole gene microarray analysis characterized by regional metastatic potential in vivo with HNSCC cell lines and identified FosL1, member of the activated protein-1 (AP-1) family, as a key molecule regulating the pathways related with regional metastasis of HNSCC. Small interfering RNA (siRNA)-mediated knockdown of FosL1 in HNSCC cells, markedly suppressed the ability of invasion and migration in vitro. In addition, short hairpin RNA (shRNA)-mediated knockdown of FosL1 significantly repressed the incidence of cervical lymph node metastases in vivo. These results suggested that FosL1 could play an important role to promote cell invasion, migration and regional metastasis of HNSCC.

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌は進行癌で発見されることが多く，予後不良である。ここ数十年の予後改善は乏しく，その大きな原因の一つは，高頻度に発生する頸部リンパ節転移を含む，転移病変の制御が困難なため治療成績が改善しないことにある。
本研究で明らかにしたFosL1を介した頸部リンパ節転移制御機構により，頸部リンパ節転移を標的とした新しい頭頸部癌治療開発につなげることが可能となり，頭頸部癌患者の予後改善に大きく寄与できると考える。

Research Products

• [Journal Article] Fibrinogen and Neutrophil-to-lymphocyte Ratio Predicts Survival in Patients with Advanced Hypopharyngeal Squamous Cell Carcinoma (2018)
  • Author(s): Kuwahara T, Takahashi H, Sano D, Matsuoka M, Hyakusoku H, Hatano T, Hiiragi Y, Oridate N.
  • Journal Title: Anticancer Res. Volume: 38 Issue: 9 Pages: 5321-5330
  • DOI: 10.21873/anticanres.12859
  • Peer Reviewed
• [Journal Article] Lymph node ratio as a prognostic factor for survival in patients with head and neck squamous cell carcinoma (2018)
  • Author(s): Sano D, Yabuki K, Takahashi H, Arai Y, Chiba Y, Tanabe T, Nishimura G, Oridate N
  • Journal Title: Auris Nasus Larynx Volume: 45 Issue: 4 Pages: 846-853
  • DOI: 10.1016/j.anl.2017.11.015
  • NAID: 130007686911
  • Peer Reviewed
• [Journal Article] Sano D, Yabuki K, Arai Y, Tanabe T, Chiba Y, Nishimura G, Takahashi H, Yamanaka S, Oridate N. The applicability of new TNM classification for humanpapilloma virus-related oropharyngeal cancer in the 8th edition of the AJCC/UICC TNM staging system in Japan: A single-centre study (2018)
  • Author(s): Sano D, Yabuki K, Arai Y, Tanabe T, Chiba Y, Nishimura G, Takahashi H, Yamanaka S, Oridate N
  • Journal Title: Auris Nasus Larynx Volume: 45 Issue: 3 Pages: 558-565
  • DOI: 10.1016/j.anl.2017.07.010
  • Peer Reviewed
• [Journal Article] Identification of human papillomavirus (HPV) 16 DNA integration and the ensuing patterns of methylation in HPV-associated head and neck squamous cell carcinoma cell lines. (2017)
  • Author(s): Takashi Hatano, Daisuke Sano, Hideaki Takahashi, Hiroshi Hyakusoku, Yasuhiro Isono, Shoko Shimada, Kae Sawakuma, Kentaro Takada, Ritsuko Oikawa, Yoshiyuki Watanabe, Hiroyuki Yamamoto, Fumio Itoh, Jeffrey N. Myers, Nobuhiko Oridate
  • Journal Title: Internal Journal of Cancer Volume: 140(7) Issue: 7 Pages: 1571-1580
  • DOI: 10.1002/ijc.30589
  • Peer Reviewed / Int'l Joint Research
• [Journal Article] JunB promotes cell invasion, migration and distant metastasis of head and neck squamous cell carcinoma (2016)
  • Author(s): Hyakusoku H, Sano D, Takahashi H, Hatano T, Isono Y, Shimada S, Ito Y, Myers JN, Oridate N
  • Journal Title: J Exp Clin Cancer Res Volume: 35 Issue: 1 Pages: 6-6
  • DOI: 10.1186/s13046-016-0284-4
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Presentation] Treatment outcome of the EXTREME regimen for recurrent or metastatic squamous cell carcinoma of head and neck (2018)
  • Author(s): Sano D, Tokuhisa M, Ichikawa Y, Oridate N
  • Organizer: The 56th annual meeting of Japan Society of Clinical Oncology
  • Int'l Joint Research
• [Presentation] Fra-1 promotes cell invasion and migration of head and neck squamous cell carcinoma (2017)
  • Author(s): 澤熊香衣，佐野大佑，高橋秀聡，百束紘，波多野孝，磯野泰大，島田翔子，高田顕太郎，折舘伸彦
  • Organizer: 第76回日本癌学会
  • Int'l Joint Research
• [Presentation] JunB plays an important role in promoting cell invasion, migration and distant metastasis through regulating matrix metalloproteinase in head and neck squamous cell carcinoma (2016)
  • Author(s): 1.Sano D, Hyakusoku H, Takahashi H, Hatano T, Isono Y, Shimada S, Sawakuma K, Myers JN, Oridate N
  • Organizer: AHNS 9th International Conference on Head and Neck Cancer
  • Place of Presentation: Seattle, WA (USA)
  • Year and Date: 2016-07-16
  • Int'l Joint Research