A novel strategy, targeting monocarboxylate transporter in head and neck cancer

• Project/Area Number: 17K16916
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Otorhinolaryngology
• Research Institution: Osaka University
• Principal Investigator: Miyabe Junji 大阪大学, 医学部附属病院, 医員 (60756831)
• Research Collaborator: Nakagawa Takashi
• Project Period (FY): 2017-04-01 – 2019-03-31
• Project Status: Completed (Fiscal Year 2018)
• Budget Amount: ¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000); Fiscal Year 2018: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2017: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: 頭頸部癌 / 乳酸トランスポーター / 放射線抵抗性 / 乳酸 / トランスポーター

Outline of Final Research Achievements

Monocarboxylate transporter 4 (MCT4) is a transmembrane protein. It is reported that MCT4 is activated by hypoxia and is associtated with radioresistance resulting in poor prognosis. I confirmed the expression of MCT4 in head and neck cancer cell lines (Fadu). I established MCT4-knockout Fadu head and neck cancer cell line using CRISPR/Cas9 system-mediated genetic engineering to confirm the malignant potential of head and neck cancer. MCT4 knockout did not affect cell proliferation and radio-sensitivity.

Academic Significance and Societal Importance of the Research Achievements

局所進行頭頸部扁平上皮癌において臓器温存を目指す標準治療は化学放射線療法である。しかし、一部の癌細胞は放射線抵抗性を示し遺残・再発の原因となり、その治療成績は十分に満足のいくものではない。治療成績の向上のためには、低酸素環境を生き延びる癌細胞を制御する新規治療法の開発が必要であり、今回低酸素環境下で発現が上昇する乳酸トランスポーターに着目し研究を行った。