Development of cancer molecular therapeutics directed to telomeres and cellular senescence svstems

• Project/Area Number: 20015047
• Research Category: Grant-in-Aid for Scientific Research on Priority Areas
• Allocation Type: Single-year Grants
• Review Section: Biological Sciences
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: SEIMIYA Hiroyuki Japanese Foundation For Cancer Research, 癌化学療法センター分子生物治療研究部, 部長 (50280623)
• Project Period (FY): 2008 – 2009
• Project Status: Completed (Fiscal Year 2009)
• Budget Amount: ¥18,000,000 (Direct Cost: ¥18,000,000); Fiscal Year 2009: ¥9,000,000 (Direct Cost: ¥9,000,000); Fiscal Year 2008: ¥9,000,000 (Direct Cost: ¥9,000,000)
• Keywords: がん / 分子標的治療 / テロメア / 細胞老化 / 細胞分裂 / 染色体 / 抗がん剤 / テロメラーゼ / ポリADP-リボシル化 / DNA損傷 / 遺伝子発現

Research Abstract

Telomeres, the capping structures of chromosome ends, work as a timing device for cellular senescence. We focused on the elomere maintenance system, which supports the immortality of human cancer cells, as a molecular target for cancer therapy. Fist, we constructed a profiling database of structural diversity in telomeres as an analytic platform of this study. By utilizing this database, we demonstrated the functional linkages between telomere/ageing regulators and sensitivities to anticancer drugs, and molecular mechanisms for the anticancer efficacy of a telomerase inhibitor. Furthermore, we discovered a pathological involvement of telomeric factors in mitotic abnormalities of a cell.

Research Products

• [Journal Article] TRF1 mediates mitotic abnormalities induced by Aurora-Aoverexpression. (2010)
  • Author(s): Ohishi, T., Hirota, T., Tsuruo, T., Seimiya, H.
  • Journal Title: Cancer Res 70 Pages: 2041-2052
  • Peer Reviewed
• [Journal Article] Visualization of G-quadruplexes by using a BODIPY-labeled macrocyclic heptaoxazole. (2010)
  • Author(s): Tera, M., Iida, K., Ikebukuro, K., Seimiya, H., Shin-Ya, K., Nagasawa, K.
  • Journal Title: Org Biomol Chem 8 Pages: 2749-2755
  • Peer Reviewed
• [Journal Article] A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor. (2010)
  • Author(s): Yashiroda, Y., Okamoto, R., Hatsugai, K., Takemoto, Y., Goshima, N., Saito, T., Hamamoto, M., Sugimoto, Y., Osada, H., Seimiya, H., Yoshida, M.
  • Journal Title: Biochem Biophys Res Comma 394 Pages: 569-573
  • Peer Reviewed
• [Journal Article] Role of insulin-like growth factor binding protein 2 in lung adenocarcinoma: IGF-independent antiapoptotic effect via caspase-3. (2010)
  • Author(s): Migita, T., Narita, T., Asaka, R., Miyagi, E., Nagano, H., Nomura, K., Matsuura, M., Satoh, Y., Okumura, S., Nakagawa, K., Seimiya, H., Ishikawa, Y.
  • Journal Title: Am J Pathol 176 Pages: 1756-1766
  • Peer Reviewed
• [Journal Article] Expression of mutant RPA in human cancer cells causes telomere shortening. (2010)
  • Author(s): Kobayashi, Y., Sato, K., Kibe, T., Seimiya, H., Nakamura, A., Yukawa, M., Tsuchiya, E., Ueno, M.
  • Journal Title: Biosci Biotechnol Biochem 74 Pages: 382-385
  • NAID: 10027551727
  • Peer Reviewed
• [Journal Article] Visualization of G-quadruplexes by using a BODIPY-labeled macrocyclic heptaoxazole (2010)
  • Author(s): Tera M
  • Journal Title: Org Biomol Chem (印刷中)
  • Peer Reviewed
• [Journal Article] A novel yeast cell-based screen identifies flavone as a tankyrase inhibitor (2010)
  • Author(s): Yashiroda Y
  • Journal Title: Biochem Biophys Res Commun 394 Pages: 569-73
  • Peer Reviewed
• [Journal Article] TRF1 mediates mitotic abnormalities induced by Aurora-A overexpression (2010)
  • Author(s): Ohishi T
  • Journal Title: Cancer Res 70 Pages: 2041-52
  • Peer Reviewed
• [Journal Article] Role of insulin-like growth factor binding protein 2 in lung adenocarcinoma : IGF-independent antiapoptotic effect via caspase-3 (2010)
  • Author(s): Migita T
  • Journal Title: Am J Pathol 176 Pages: 1756-66
  • Peer Reviewed
• [Journal Article] Expression of mutant RPA in human cancer cells causes telomere shortening (2010)
  • Author(s): Kobayashi Y
  • Journal Title: Biosci Biotechnol Biochem 74 Pages: 382-5
  • Peer Reviewed
• [Journal Article] Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer. (2009)
  • Author(s): McCabe, N., Cerone, M.A., Ohishi, T., Seimiya, H., Lord, C.J., Ashworth, A.
  • Journal Title: Oncogene 28 Pages: 1465-1470
  • Peer Reviewed
• [Journal Article] De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. (2009)
  • Author(s): Mashima, T., Seimiya, H., Tsuruo, T.
  • Journal Title: Br J Cancer 100 Pages: 1369-1372
  • Peer Reviewed
• [Journal Article] Promotion of glioma cell survival by acyl-CoA synthetase 5 under extracellular acidosis conditions. (2009)
  • Author(s): Mashima, T., Sato, S., Sugimoto, Y., Tsuruo, T., Seimiya, H.
  • Journal Title: Oncogene 28 Pages: 9-19
  • Peer Reviewed
• [Journal Article] Acyl-CoA synthetase as a cancer survival factor: its inhibition enhances the efficacy of etoposide. (2009)
  • Author(s): Mashima, T., Sato, S., Okabe, S., Miyata, S., Matsuura, M., Sugimoto, Y., Tsuruo, T., Seimiya, H.
  • Journal Title: Cancer Sci 100 Pages: 1556-1562
  • NAID: 10027193846
  • Peer Reviewed
• [Journal Article] Acyl-CoA synthetase as a cancer survival factor : its inhibition enhances the efficacy of etoposide (2009)
  • Author(s): Mashima T
  • Journal Title: Cancer Sci 100 Pages: 1556-62
  • Peer Reviewed
• [Journal Article] De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy (2009)
  • Author(s): Mashima T
  • Journal Title: Br J Cancer 100 Pages: 1369-72
  • Peer Reviewed
• [Journal Article] Acyl-CoA synthetase as a cancer survival factor:its inhibition enhances the efficacy of etoposide. (2009)
  • Author(s): Mashima T
  • Journal Title: Cancer Science (印刷中)
  • Peer Reviewed
• [Journal Article] De novo fatty-acid synthesis and related pathways as molecular targets for cancer therapy. (2009)
  • Author(s): Mashima T
  • Journal Title: British Journal of Cancer 100 Pages: 1369-1372
  • Peer Reviewed
• [Journal Article] Promotion of glioma cell survival by ancyl-CoA synthetase 5 under extracellular acidosis (2009)
  • Author(s): Mashima T
  • Journal Title: Oncogene 28 Pages: 9-19
  • Peer Reviewed
• [Journal Article] Targeting Tankyrase 1 as a therapeutic strategy for BRCA-associated cancer. (2009)
  • Author(s): MaCabe N
  • Journal Title: Oncogene 28 Pages: 1465-1470
  • Peer Reviewed
• [Journal Article] Telomere elongation by a mutant tankyrase 1 without TRF1 poly(ADP-ribosyl)ation. (2008)
  • Author(s): Muramatsu, Y., Tahara, H., Ono, T., Tsuruo, T., Seimiya, H.
  • Journal Title: Exp Cell Res 314 Pages: 1115-1124
  • Peer Reviewed
• [Journal Article] ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. (2008)
  • Author(s): Migita, T., Narita, T., Nomura, K., Miyagi, E., Inazuka, F., Matsuura, M., Ushijima, M., Mashima, T., Seimiya, H., Satoh, Y., Okumura, S., Nakagawa, K., Ishikawa, Y.
  • Journal Title: Cancer Res 68 Pages: 8547-8554
  • Peer Reviewed
• [Journal Article] ATP citrate lyase: activation and therapeutic implications in non-small cell lung cancer. (2008)
  • Author(s): Mashima T
  • Journal Title: Cancer Research 68 Pages: 8547-8554
  • Peer Reviewed
• [Presentation] 癌の内用放射線治療薬剤の開発を目指した放射性ヨウ素標識テロメラーゼ阻害剤の合成と基礎的評価 (2010)
  • Author(s): 吉田衛
  • Organizer: 日本薬学会第130年会
  • Place of Presentation: 岡山
  • Year and Date: 2010-03-28
• [Presentation] V-ATPase inhibitors, concanamycin B, and Bafilomycin induce the reduction of G-tail length and TRF2 foci (2010)
  • Author(s): Tahara H
  • Organizer: AACR Special Conference on the Role of Telomerase and Telomeres in Cancer Research
  • Place of Presentation: Fort Worth, USA
  • Year and Date: 2010-02-28
• [Presentation] TRF1 mediates mitotic abnormalities induced by Aurora-A overexpression. (2010)
  • Author(s): Seimiya, H., Ohishi, H., Hirota, T., Tsuruo, T.
  • Organizer: AACR Special Conference on the Role of Telomerase and Telomeres in Cancer Research
  • Place of Presentation: Fort Worth, USA
  • Year and Date: 2010-02-27
• [Presentation] TRF1 mediates mitotic abnormalities induced by Aurora-A overexpression (2010)
  • Author(s): 清宮啓之
  • Organizer: AACR Special Conference on the Role of Telomerase and Telomeres in Cancer Research
  • Place of Presentation: Fort Worth, USA
  • Year and Date: 2010-02-27
• [Presentation] Telomere fingerprinting for prediction of anticancer drug sensitivities (2010)
  • Author(s): 清宮啓之
  • Organizer: AACR/JCA Joint Conference : Cancer Genomics, Epigenomics and the Development of Novel Therapeutics
  • Place of Presentation: Hawaii, USA
  • Year and Date: 2010-02-09
• [Presentation] がん分子標的治療探索とトランスレーショナルリサーチへの展開 (2010)
  • Author(s): 清宮啓之
  • Organizer: 中国・四国広域がんプロ養成コンソーシアム・徳島大学大学院セミナー
  • Place of Presentation: 徳島
  • Year and Date: 2010-02-03
• [Presentation] テロメア制御因子の新たな機能と阻害剤探索 (2010)
  • Author(s): 清宮啓之
  • Organizer: 広島大学大学院医歯薬学総合研究科セミナー
  • Place of Presentation: 広島
  • Year and Date: 2010-01-25
• [Presentation] テロメア伸長刺激に対するがん細胞の転写応答 (2009)
  • Author(s): 平島匡太郎
  • Organizer: 第32回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2009-12-09
• [Presentation] Telomere maintenance systems as anticancer targets. (2009)
  • Author(s): Seimiya, H.
  • Organizer: The 14th Japanese Foundation for Cancer Research-International Symposium on Cancer Chemotherapy
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2009-12-02
• [Presentation] Telomere maintenance systems as anticancer targets (2009)
  • Author(s): 清宮啓之
  • Organizer: The 14th Japanese Foundation for Cancer Research-International Symposium on Cancer Chemotherapy
  • Place of Presentation: Tokyo, Japan
  • Year and Date: 2009-12-02
• [Presentation] Involvement of TRF1 in mitotic abnormalities led by Aurora A overexpression (2009)
  • Author(s): 大石智一
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-03
• [Presentation] Novel role for multiple TRF1 binding sites of tankyrase 1 in telomere elongation (2009)
  • Author(s): 村松由起子
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Visualizing telomeric function of tankyrase 1 and its application to inhibitor screening (2009)
  • Author(s): 初谷香織
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2009-10-01
• [Presentation] Telomere fingerprinting for global prediction of anticancer drug sensitivities (2009)
  • Author(s): Seimiya, H.
  • Organizer: Japanese-German Cancer Workshop
  • Place of Presentation: Hamburg, Germany
  • Year and Date: 2009-09-17
• [Presentation] テロメアを標的としたがん治療 (2009)
  • Author(s): 清宮啓之
  • Organizer: 第2回富山ライフサイエンスシンポジウム～がんの基礎研究と臨床研究のかけわたし～
  • Place of Presentation: 富山
  • Year and Date: 2009-07-25
• [Presentation] Telomere Fingerprint Databaseの構築と薬剤反応性研究への応用 (2009)
  • Author(s): 清宮啓之、村松由起子、田原栄俊、矢守隆夫、鶴尾隆
  • Organizer: 第13回日本がん分子標的治療学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2009-06-25
• [Presentation] Telomere Fingerprint Database の構築と薬剤反応性研究への応用 (2009)
  • Author(s): 清宮啓之
  • Organizer: 第13回日本がん分子標的治療学会学術集会
  • Place of Presentation: 徳島
  • Year and Date: 2009-06-25
• [Presentation] Telomere fingerprinting for global prediction of anticancer drug sensitivities. (2009)
  • Author(s): Seimiya, H., Muramatsu, Y., Tokunaga, S., Tahara, H., Ueno, M., Yamori, T., Tsuruo, T.
  • Organizer: Cold Spring Harbor Laboratory Meeting on Telomeres & Telomerase.
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2009-04-30
• [Presentation] Telomere fingerprinting for global prediction of anticancer drug sensitivities (2009)
  • Author(s): 清宮啓之
  • Organizer: Cold Spring Harbor Laboratory Meeting on Telomeres & Telomerase
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2009-04-30
• [Presentation] Involvement of TRF1 in the mitotic abnormalities led by Aurora A overexpression (2009)
  • Author(s): 大石智一
  • Organizer: Cold Spring Harbor Laboratory Meeting on Telomeres & Telomerase
  • Place of Presentation: Cold Spring Harbor, USA
  • Year and Date: 2009-04-30
• [Presentation] テロメアの構造的多様性を起点とした薬剤反応性研究 (2009)
  • Author(s): 清宮啓之
  • Organizer: 理化学研究所ケミカルバイオロジー研究領域勉強会
  • Place of Presentation: 和光
  • Year and Date: 2009-04-22
• [Presentation] ポリ(ADP-リボシル)化酸素タンキラーゼ1の自己多量体化によるテロメア機能の調節 (2009)
  • Author(s): 初谷香織
  • Organizer: 日本薬学会第129年会
  • Place of Presentation: 京都
  • Year and Date: 2009-03-26
• [Presentation] Telomere fingerprinting and its application to drug sensitivity studies (2009)
  • Author(s): Seimiya, H.
  • Organizer: The 9th Korea-Japan Symposium on Cancer and Ageing Research.
  • Place of Presentation: Damyang, Korea
  • Year and Date: 2009-03-12
• [Presentation] Telomere fingerprinting and its application to drug sensitivity studies (2009)
  • Author(s): 清宮啓之
  • Organizer: The 9th Korea-Japan Symposium on Cancer and Ageing Reseach
  • Place of Presentation: 韓国・Damyang
  • Year and Date: 2009-03-12
• [Presentation] テロメア・老化関連分子を標的とした新規がん化学療法の開発 (2009)
  • Author(s): 清宮啓之
  • Organizer: 第1回佐賀大学先端研究センター研究推進部門セミナー「がん分子標的療法の新展開」
  • Place of Presentation: 佐賀
  • Year and Date: 2009-02-27
• [Presentation] テロメア動態制御ネットワークの解明と薬剤反応性研究への応用・岩手医科大学 (2009)
  • Author(s): 清宮啓之
  • Organizer: 化学療法基盤情報支援班共催シンポジウム「抗がん剤創薬の新たな展開」
  • Place of Presentation: 岩手
  • Year and Date: 2009-01-16
• [Presentation] テロメア動態制御ネットワークの解明と薬剤反応性研究への応用 (2009)
  • Author(s): 清宮啓之
  • Organizer: 岩手医科大学・化学療法基盤情報支援班共催シンポジウム「抗がん剤創薬の新たな展開」
  • Place of Presentation: 岩手
  • Year and Date: 2009-01-16
• [Presentation] テロメア伸長がもたらすがん細胞の遺伝子発現変化 (2008)
  • Author(s): 平島匡太郎
  • Organizer: 第31回日本分子生物学会年会(第81回日本生物化学大会合同大会)
  • Place of Presentation: 神戸
  • Year and Date: 2008-12-11
• [Presentation] TRF1 mediates mitotic abnormalities induced by Aurora A overexpression. (2008)
  • Author(s): 大石智一
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-29
• [Presentation] Construction of the Telomere Fingerprint Database, a novel platform for telomere dynamics and drug sensitivity studies. (2008)
  • Author(s): 清宮啓之、村松由起子、田原栄俊、上野勝、矢守隆夫、鶴尾隆
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2008-10-28
• [Presentation] Tankyrase 1 suppresses oncogene-induced mitotic abnormalities. (2008)
  • Author(s): Seimiya, H., Ohishi, T., Tsuruo, T.
  • Organizer: EMBO Conference on Telomeres and the DNA Damage Response
  • Place of Presentation: Villars-sur-Ollon, Switzerland
  • Year and Date: 2008-09-18
• [Presentation] Tankyrase 1 suppresses oncogene-induced mitotic abnormalities. (2008)
  • Author(s): 清宮啓之
  • Organizer: 欧州EMBOカンファレンス 「Telomeres and the DNA Damage Response」
  • Place of Presentation: スイス・Villars-sur-Ollon
  • Year and Date: 2008-09-18
• [Presentation] 細胞分裂におけるテロメア結合蛋白質の新たな機能 (2008)
  • Author(s): 清宮啓之
  • Organizer: 第26回日本ヒト細胞学会学術集会
  • Place of Presentation: 東京
  • Year and Date: 2008-08-30
• [Book] Tanlyrase l,telo,ere-binding proteins, and inhibitors.(Hiyama, K., editor., Telomeres and Telomerase in Cancer.) (2009)
  • Author(s): Seimiya, H., Tsuruo T.
  • Publisher: Humana Press
• [Book] Tankyrases.(Schwab, M., editor., Encyclopedia of Cancer.2nd ed.) (2009)
  • Author(s): Seimiya, H.
  • Publisher: Springer
• [Book] Tankyrase 1, telomere-binding proteins, and inhibitors. In "Telomeres and telomerase in cancer"(Hiyama K Ed.) (2009)
  • Author(s): Seimiya H
  • Publisher: Humana Press
• [Book] Tankyrases. In "Encyclopedia of cancer 2nd ed."(Schwab M Ed.) (2009)
  • Author(s): Seimiya H
  • Publisher: Springer
• [Book] Telomeres and Telomerase in Cancer, Edited by Hiyama K, 「Tankyrase 1, telomere-binding proteins, and inhibitors」 (2009)
  • Author(s): Seimiya H
  • Publisher: Humana Press
• [Book] 生命の科学(テロメア長の制御機構, 59) (2008)
  • Author(s): 清宮啓之
  • Publisher: 医学書院
• [Remarks] 和文
  • URL: http://www.jfcr.or.jp/laboratory/ccc/molecularbiotherapy/index.html
• [Remarks] 英文
  • URL: http://www.jfenonjp/laboratory/english/ccc/molecularbiotherapy/index.html
• [Remarks]
  • URL: http://www.jfcr.or.jp/laboratory/ccc/molecularbiotherapy/index.html
• [Remarks]
  • URL: http://ww.jfcr.or.jp/laboratory/ccc/molecularbiotherapy/index.html