Suppression of telomerase-independent telomere maintenance mechanism in cancer cells

• Project/Area Number: 26710006
• Research Category: Grant-in-Aid for Young Scientists (A)
• Allocation Type: Partial Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Tokyo University of Science (2017); Kyoto University (2014-2016)
• Principal Investigator: Sadaie Mahito 東京理科大学, 理工学部応用生物科学科, 准教授 (70415173)
• Research Collaborator: Ishikawa Fuyuki 京都大学, 大学院生命科学研究科, 教授
• Project Period (FY): 2014-04-01 – 2018-03-31
• Project Status: Completed (Fiscal Year 2017)
• Budget Amount: ¥22,230,000 (Direct Cost: ¥17,100,000、Indirect Cost: ¥5,130,000); Fiscal Year 2017: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2016: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2015: ¥5,460,000 (Direct Cost: ¥4,200,000、Indirect Cost: ¥1,260,000); Fiscal Year 2014: ¥5,850,000 (Direct Cost: ¥4,500,000、Indirect Cost: ¥1,350,000)
• Keywords: 遺伝子 / がん / ゲノム / トランスレーショナルリサーチ / 癌 / 老化

Outline of Final Research Achievements

Telomere maintenance is required for continuous proliferation of cancer cells. Many sarcoma cells maintain telomeres without telomerase. This telomerase-independent mechanism is known as ALT (alternative lengthening of telomeres). In the present study, we sought to develop method(s) by which proliferation of ALT cancer cells can be suppressed. We first isolated proteins that are specifically bind chromosomal DNA in ALT cells. These proteins can be a molecular target for suppressing ALT cell’s growth. We also identified a compound that inhibit proliferation of ALT cells but not that of normal cells. The compound is converted to genotoxic form and induced DNA damage in ALT cells.