The role and functional analysis of the AP-1 family in cervical lymph node metastasis of head and neck carcinoma

• Project/Area Number: 19K09851
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56050:Otorhinolaryngology-related
• Research Institution: Yokohama City University
• Principal Investigator: HYAKUSOKU Hiroshi 横浜市立大学, 医学研究科, 客員研究員 (80712794)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Project Status: Completed (Fiscal Year 2022)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2020: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000); Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: 頭頸部癌 / 頸部リンパ節転移 / 頭頚部癌

Outline of Research at the Start

頭頸部癌は，ここ数十年予後の改善は乏しい．大きな原因の一つとして，頭頸部癌が高頻度に転移病変を有し，その制御が困難なため治療成績が改善しないことがあげられる．申請者は同所性頭頸部癌モデルを用いて，頭頸部癌の頸部リンパ節転移関連候補遺伝子としてAP-1遺伝子群を同定し，さらに，FosL1が細胞増殖能，遊走能および頸部リンパ節転移能を促進することを明らかにした．本研究の目的はFosL1およびAP-1遺伝子群により発現を制御され，浸潤能，遊走能，頸部リンパ節転移能の変化に直接関与する因子を網羅的解析手法により探索し，臨床検体と比較検討することで，頭頸部癌の新たな診断法や治療標的を同定することである．

Outline of Final Research Achievements

Head and neck carcinoma has a high frequency of metastatic lesions, and is greatly related to death because it is difficult to control. The applicant combined the results of cervical lymph node metastasis in an orthotopic mouse model using human head and neck carcinoma cell lines with whole gene microarray and key node analysis to identify the AP-1 family as a candidate related to cervical lymph node metastasis in head and neck carcinoma. Among them, FosL1 was identified to be involved in cell proliferation and migration in human head and neck carcinoma cell lines. Furthermore, we identified that the suppression of FosL1 decreased cervical lymph node metastasis potential in human head and neck carcinoma cell lines. The suppression of FosL1 suggested to decrease the cervical lymph node metastatic potential in head and neck carcinoma.

Academic Significance and Societal Importance of the Research Achievements

頭頸部癌は高頻度に転移病変を有し，その制御が困難なため死に大きく関わる疾患である．申請者は,FosL1が頭頸部癌の頸部リンパ節転移に関わることを同定し，FosL1を抑制することで，頸部リンパ節転移を抑制できることを示した．
今後，FosL1に関わるパスウェイを抑制するような新薬の開発によって，頭頸部癌患者の治療成績の向上に寄与する可能性や，事前に頸部リンパ節転移を起こしやすいか否かを推測できる可能性があり，頭頸部癌患者に対するオーダーメイド治療が可能となり得る．

Research Products

• [Journal Article] FosL1 Regulates Regional Metastasis of Head and Neck Squamous Cell Carcinoma by Promoting Cell Migration, Invasion, and Proliferation (2021)
  • Author(s): Hiroshi Hyakusoku, Kae Sawakuma, Daisuke Sano, Hideaki Takahashi, Takashi Hatano, Kaname Sato, Yasuhiro Isono, Shoko Shimada, Kentaro Takada, Tatsu Kuwahara, Yoshihiro Aizawa, Nobuhiko Oridate
  • Journal Title: Anticancer research Volume: 41 Issue: 7 Pages: 3317-3326
  • DOI: 10.21873/anticanres.15119
  • Peer Reviewed / Open Access / Int'l Joint Research