Development of cancer molecular therapeutics that targets telomere-regulating factors

2012 Fiscal Year Final Research Report

• Project/Area Number: 22300341
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: SEIMIYA Hiroyuki 公益財団法人がん研究会, がん化学療法センター分子生物治療研究部, 部長 (50280623)
• Project Period (FY): 2010 – 2012
• Keywords: テロメア / テロメラーゼ / がん / 不死化 / 細胞老化 / 分子標的治療 / 染色体

Research Abstract

This study aims to design a telomere-directed cancer therapy. As main results, we found that G-quadruplex ligands induce DNA damage and transcriptional aberration and inhibit growth of glioma stem cells. We also found that self-assembly of tankyrase, a positive regulator of telomere elongation represses its function. Furthermore, we found that cancer cells that exhibit low expression of telomere-related factors, WRN and POT1, are sensitive to anti-microtubule drugs. These results would be applicable to development of new cancer chemotherapy

Research Products

• [Journal Article] Development of a gene expression database and related analysis programs for evaluation of anticancer compounds (2013)
  • Author(s): Ushijima, M., Mashima, T., Tomida, A., Dan, S., Saito, S., Furuno, A., Tsukahara, S., Seimiya, H., Yamori, T., Matsuura, M
  • Journal Title: Cancer Sci Volume: 104 Pages: 360-8
  • Peer Reviewed
• [Journal Article] Inhibition of ATP citrate lyase induces an anticancer effect via reactive oxygen species: AMPK as a predictive biomarker for therapeutic impact (2013)
  • Author(s): Migita, T., Okabe, S., Ikeda, K., Igarashi, S., Sugawara, S., Tomida, A., Taguchi, R., Soga, T., Seimiya, H
  • Journal Title: Am J Pathol Volume: 182 Pages: 1800-1810
  • Peer Reviewed
• [Journal Article] Evaluation of the interaction between long telomeric DNA and macrocyclic hexaoxazole (6OTD) dimer of a G-quadruplex ligand (2013)
  • Author(s): Iida, K., Majima, S., Nakamura, T., Seimiya, H., Nagasawa, K
  • Journal Title: Molecules Volume: 18 Pages: 4328-4341
  • Peer Reviewed
• [Journal Article] Tankyrase-1 function at telomeres and during mitosis is regulated by Polo-like kinase-1-mediated phosphorylation (2012)
  • Author(s): Ha, G. H., Kim, H. S., Go, H., Lee, H., Seimiya, H., Chung, D. H., Lee, C. W
  • Journal Title: Cell Death Differ Volume: 19 Pages: 321-332
  • Peer Reviewed
• [Journal Article] Telomestatin impairs glioma stem cell survival and growth through the disruption of telomeric G-quadruplex and inhibition of the proto-oncogene, c-Myb (2012)
  • Author(s): Miyazaki, T., Pan, Y., Joshi, K., Purohit, D., Hu, B., Demir, H., Mazumder, S., Okabe, S., Yamori, T.,Viapiano, M., Shin-ya, K., Seimiya, H., Nakano, I
  • Journal Title: Clin Cancer Res Volume: 18 Pages: 1268-1280
  • Peer Reviewed
• [Journal Article] A caged ligand for a telomeric G-quadruplex (2012)
  • Author(s): Nakamura, T., Iida, K., Tera, M., Shin-ya, K., Seimiya, H., Nagasawa, K
  • Journal Title: Chembiochem Volume: 13 Pages: 774-777
  • Peer Reviewed
• [Journal Article] JBIR-120: a new growth inhibitor of hormone-refractory prostate cancer cells (2012)
  • Author(s): Kawahara, T., Hosoya, T., Tsukamoto, M., Okabe, S., Yamamura, H., Hayakawa, M., Seimiya, H., Takagi, M., Shin-Ya, K
  • Journal Title: J Antibiot Volume: 65 Pages: 373-375
  • Peer Reviewed
• [Journal Article] et al., HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle (2012)
  • Author(s): Deardorff, M.A., Seimiya, H.
  • Journal Title: Nature Volume: 489 Pages: 313-317
  • Peer Reviewed
• [Journal Article] Molecular pharmacological approach reveals potential new strategies to suppress androgen receptor signaling in prostate cancer (2011)
  • Author(s): Mashima, T., Okabe, S., Seimiya, H
  • Journal Title: Mol Cell Pharmacol Volume: 3 Pages: 7-12
  • Peer Reviewed
• [Journal Article] Fission yeast pot1 and recQ helicase are required for efficient chromosome segregation (2011)
  • Author(s): Takahashi, K., Imano, R., Kibe, T., Seimiya, H., Muramatsu, Y., Kawabata, N., Tanaka, G., Matsumoto, Y., Hiromoto, T., Koizumi, Y., Nakazawa, N., Yanagida, M., Yukawa, M., Tsuchiya, E., Ueno, M
  • Journal Title: Mol Cell Biol Volume: 31 Pages: 95-506
  • Peer Reviewed
• [Journal Article] Role of acyl-CoA synthetases in glioma cell survival and its therapeutic implication (2011)
  • Author(s): Mashima, T., Seimiya, H
  • Journal Title: Tumors of the Central Nervous System Volume: 1 Pages: 337-340
  • Peer Reviewed
• [Journal Article] Tankyrase-1 assembly to large protein complexes blocks its telomeric function (2010)
  • Author(s): Hatsugai, K., Ohishi, T., Sugimoto, Y., Seimiya, H
  • Journal Title: FEBS Lett Volume: 584 Pages: 3885-3890
  • 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 Volume: 74 Pages: 382-385
  • Peer Reviewed
• [Journal Article] Pharmacological targeting of constitutively active truncated androgen receptor by nigericin and suppression of hormone-refractory prostate cancer cell growth (2010)
  • Author(s): Mashima, T., Okabe, S., Seimiya, H
  • Journal Title: Mol Pharmacol Volume: 78 Pages: 846-854
  • 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 Volume: 176 Pages: 1756-1766
  • Peer Reviewed
• [Journal Article] TRF1 mediates mitotic abnormalities induced by Aurora-A overexpression (2010)
  • Author(s): Ohishi, T., Hirota, T., Tsuruo, T., Seimiya, H
  • Journal Title: Cancer Res Volume: 70 Pages: 2041-2052
  • Peer Reviewed
• [Journal Article] Generation of induced pluripotent stem cells from human terminally differentiated circulating T cells (2010)
  • Author(s): Seki, T., Yuasa, S., Oda, M., Egashira, T., Yae, K., Kusumoto, D., Nakata, H., Tohyama, S., Hashimoto, H., Kodaira, M., Okada, Y., Seimiya, H., Fusaki, N., Hasegawa, M., Fukuda, K
  • Journal Title: Cell Stem Cell Volume: 7 Pages: 11-14
  • 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 Volume: 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 Commun Volume: 394 Pages: 569-573
  • Peer Reviewed
• [Journal Article] Telomere length influences cancer cell differentiation in vivo
  • Author(s): Hirashima,K., Migita,T., Sato, S., Muramatsu, Y., Ishikawa,Y., Seimiya, H
  • Journal Title: Mol Cell Biol, in press
  • Peer Reviewed
• [Presentation] Targeting glioma stem cells by G-quadruplex ligands (2013)
  • Author(s): Seimiya, H
  • Organizer: 第9回日米合同癌会議
  • Place of Presentation: (Ninth AACR-JCA Joint Conference, Breakthroughs in Basic and Translational Cancer Research) (Hawaii, USA)
  • Year and Date: 20130221-25
• [Presentation] TRF1 regulates the microtubule-kinetochore attachment and contributes to proper chromosome segregation (2013)
  • Author(s): Seimiya, H
  • Organizer: 1st International Symposium on Protein Modifications in Pathogenic Dysregulation of Signaling
  • Place of Presentation: (東京)
  • Year and Date: 20130201-02
• [Presentation] Targeting glioma stem cells by G-quadruplex ligands (2012)
  • Author(s): Seimiya, H
  • Organizer: 2nd Japanese-French Cancer Workshop(招待講演)
  • Place of Presentation: (鳴門)
  • Year and Date: 20121128-1201
• [Presentation] TRF1 regulates the microtubule-kinetochore attachment and contributes to proper chromosome segregation (2012)
  • Author(s): Seimiya, H
  • Organizer: EMBO Conference on Telomeres and the DNA Damage Response
  • Place of Presentation: (L'Isle sur la Sorgue, France)
  • Year and Date: 20121002-06
• [Presentation] Targeting glioma stem cells by G-quadruplex ligands (2012)
  • Author(s): Seimiya, H
  • Organizer: 第71回日本癌学会学術総会International Session(招待講演)
  • Place of Presentation: (札幌)
  • Year and Date: 20120919-21
• [Presentation] Regulation of chromosome segregation by a telomeric protein (2012)
  • Author(s): Seimiya, H
  • Organizer: The 11th Korea-Japan-Germany Joint Symposium on Cancer and Ageing Research(招待講演)
  • Place of Presentation: (Gyeongju, Korea)
  • Year and Date: 20120705-07
• [Presentation] ポリ(ADP-リボシル)化酵素タンキラーゼによる細胞制御と阻害剤開発 (2012)
  • Author(s): 清宮啓之
  • Organizer: 慶應義塾大学先端医科学研究所セミナー(招待講演)
  • Place of Presentation: (東京)
  • Year and Date: 2012-10-11
• [Presentation] Regulation of chromosome segregation by a telomeric protein TRF1 (2011)
  • Author(s): Seimiya, H
  • Organizer: 日仏がん研究ワークショップ(招待講演)
  • Place of Presentation: (フランス・モンペリエ)
  • Year and Date: 2011-11-22
• [Presentation] Telomere fingerprinting for drug sensitivity studies and cancer cell biology (2011)
  • Author(s): Seimiya, H
  • Organizer: ニース大学招待セミナー(招待講演)
  • Place of Presentation: (フランス・ニース)
  • Year and Date: 2011-11-21
• [Presentation] がん治療応用を目指したテロメア研究の現況 (2011)
  • Author(s): 清宮啓之
  • Organizer: 医薬ライセンシング協会 第236回月例会(招待講演)
  • Place of Presentation: (東京)
  • Year and Date: 2011-11-15
• [Presentation] ポリ(ADP-リボシル)化酵素タンキラーゼ1の新たな分子機能 (2011)
  • Author(s): 清宮啓之
  • Organizer: 第84回日本生化学会大会シンポジウム「ADP-リボシル化によるシグナル伝達制御」(招待講演)
  • Place of Presentation: (京都)
  • Year and Date: 2011-09-21
• [Presentation] テロメアを起点とした創薬シーズ開発と新たながん生物学研究への展開 (2011)
  • Author(s): 清宮啓之
  • Organizer: 愛媛大学 第4回分子病態医学セミナー(招待講演)
  • Place of Presentation: (松山)
  • Year and Date: 2011-09-07
• [Presentation] Development of telomerase inhibitors and their application to anticancer therapeutics (2010)
  • Author(s): Seimiya, H
  • Organizer: Pacifichem 2010
  • Place of Presentation: (Hawaii, USA)
  • Year and Date: 20101215-20
• [Presentation] 細胞分裂の異常を媒介するテロメア蛋白質 (2010)
  • Author(s): 清宮啓之
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会・ワークショップ
  • Place of Presentation: (神戸)
  • Year and Date: 20101207-10
• [Presentation] がん治療応用をめざしたテロメア研究の新展開 (2010)
  • Author(s): 清宮啓之
  • Organizer: 東京大学医科学研究所・学友会セミナー・GCOE特別セミナー
  • Place of Presentation: (東京)
  • Year and Date: 2010-07-26
• [Remarks]
  • URL: http://www.jfcr.or.jp/chemotherapy/department/molecular_biotherapy/index.html
• [Remarks] アウトリーチ活動・支援活動 清宮啓之, がんとは何でしょう? 新学術領域研究「がん研究分野の特性等を踏まえた支援活動」青少年・市民公開講座?いま知っておきたい「がん」のこと?(福島), 平成23年9月17日
• [Remarks] 清宮啓之, がん研究基礎セミナー「新薬の原石をもとめて ?抗がん剤・化合物スクリーニング?」, 平成24年度がん若手研究者ワークショップ(蓼科), 平成24年9月5-8日