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p53制御経路の網羅的解析による腫瘍細胞の特性の解明と治療法の開発

Publicly

Project AreaConquering cancer through neo-dimensional systems understanding
Project/Area Number 16H01566
Research Category

Grant-in-Aid for Scientific Research on Innovative Areas (Research in a proposed research area)

Allocation TypeSingle-year Grants
Review Section Complex systems
Research InstitutionThe University of Tokyo

Principal Investigator

松田 浩一  東京大学, 大学院新領域創成科学研究科, 教授 (90401257)

Project Period (FY) 2016-04-01 – 2018-03-31
Project Status Completed (Fiscal Year 2017)
Budget Amount *help
¥10,400,000 (Direct Cost: ¥8,000,000、Indirect Cost: ¥2,400,000)
Fiscal Year 2017: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2016: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Keywordsp53 / 癌 / がん / CRISPR/CAS9 / ゲノム解析
Outline of Annual Research Achievements

癌抑制遺伝子p53はヒト癌の約半数で変異が認められ発ガン過程において最も重要な遺伝子です。殆どの癌で転写因子としてのp53の機能が失活することから、p53変異細胞の特性を明らかにすることで、癌細胞が共通して持つ特徴、がんのアキレス腱を知ることが可能となる。本研究によって、p53変異細胞の特性を明らかとすることによって、癌細胞に普遍的に効果を示す治療法の開発を最終的な目標である。
我々はこれまでp53によって発現誘導される遺伝子群の解析を継続して実施し、p53を介した癌化抑制機構の解明を進めてきた。今回マウス24臓器における網羅的遺伝子解析の結果、p53によって5000以上の遺伝子が制御されることを明らかとした(Ebiomedicine 2017, oncotarget 2017)。さらにゲノム編集技術によるp53活性型マウスの作成と遺伝子発現解析、CRISPR/CAS9ライブラリーを用いた合成致死遺伝子のスクリーニング及びヒトがん組織、細胞株の発現情報データなどの統合的解析を実施した。これらの研究によって、p53を介したアミノ酸代謝制御(Sci. Adv. 2017)、アポトーシス(Neoplasia2017)、転移浸潤(Oncotarget2017, IJO 2017)や免疫応答制御(Sci Rep. 2017)などの発がん抑制メカニズムを明らかとした。さらにCRISPR/CAS9によるgRNAライブラリースクリーニングによるp53と合成致死に働く経路の同定及びp53によるマイクロバイオーム制御機構も明らかとした。これらの研究成果は、p53による遺伝子制御機構の全貌の解明及び新規治療法の開発につながると期待される。

Research Progress Status

29年度が最終年度であるため、記入しない。

Strategy for Future Research Activity

29年度が最終年度であるため、記入しない。

Report

(2 results)
  • 2017 Annual Research Report
  • 2016 Annual Research Report

Research Products

(30 results)

All 2018 2017 2016

All Journal Article Presentation

  • [Journal Article] Deep whole-genome sequencing reveals recent selection signatures linked to evolution and disease risk of Japanese2018

    • Author(s)
      Okada Yukinori、Momozawa Yukihide、Sakaue Saori、Kanai Masahiro、Ishigaki Kazuyoshi、Akiyama Masato、Kishikawa Toshihiro、Arai Yasumichi、Sasaki Takashi、Kosaki Kenjiro、Suematsu Makoto、Matsuda Koichi、Yamamoto Kazuhiko、Kubo Michiaki、Hirose Nobuyoshi、Kamatani Yoichiro
    • Journal Title

      Nature Communications

      Volume: 9 Pages: 1631-1631

    • DOI

      10.1038/s41467-018-03274-0

    • NAID

      120006551756

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Multiancestry genome-wide association study of 520.000 subjects identifies 32 loci associated with stroke and stroke subtypes.2018

    • Author(s)
      Malik R, Chauhan G, Wakai K, Weir D, Williams SR, Wolfe CDA, Wong Q, Xu H, Yamaji T, Sanghera DK, Melander O, Jern C, Strbian D, Fernandez-Cadenas I, Longstreth WT Jr, Rolfs A, Hata J, Woo D, Rosand J, Pare G, Hopewell JC, Saleheen D, Stefansson K, Worral
    • Journal Title

      Nature Genetics

      Volume: 50 Issue: 4 Pages: 524-537

    • DOI

      10.1038/s41588-018-0058-3

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] GWAS identifies two novel colorectal cancer loci at 16q24.1 and 20q13.12.2018

    • Author(s)
      Tanikawa C, Kamatani Y, Takahashi A, Nagayama S, Mimori K, Mori M, Yasuda J, Tsuboi A, Shimizu A, Sasaki M, Yamaji T, Tsugane S, Naito M, Wakai K, Koyama T, Takezaki T, Yuji K, Murakami Y, Nakamura Y, Matsuda K, et al.
    • Journal Title

      Carcinogenesis

      Volume: Epub Pages: 652-660

    • DOI

      10.1093/carcin/bgy026

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide association study identifies seven novel susceptibility loei for primary open-angle glaucoma2018

    • Author(s)
      Shiga Y, Akiyama M, Nishiguchi K M, Sato K, Shimozawa N, Takahashi A, Momozawa Y, Hirata M, Matsuda K, Yamaji T, Iwasaki M, Tsugane S, Oze I, Mikami H, Naito M, Wakai K, Yoshikawa M, Miyake M, Yanaka T, et al.
    • Journal Title

      Human Molecular Genetics

      Volume: 27 Issue: 8 Pages: 1486-1496

    • DOI

      10.1093/hmg/ddy053

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Citrullination of RGG Motifs in FET Proteins by PAD4 Regulates Protein Aggregation and ALS Susceptibility.2018

    • Author(s)
      Tanikawa Chizu、Ueda Koji、Suzuki Akari、Iida Aritoshi、Nakamura Ryoichi、Atsuta Naoki、Tohnai Genki、Sobue Gen、Saichi Naomi、Momozawa Yukihide、Kamatani Yoichiro、Kubo Michiaki、Yamamoto Kazuhiko、Nakamura Yusuke、Matsuda Koichi
    • Journal Title

      Cell Rep

      Volume: 22 Pages: 1473-1483

    • DOI

      10.1016/j.celrep.2018.01.031

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Genetic analysis of quantitative traits in the Japanese population links cell types to complex human diseases2018

    • Author(s)
      Kanai M, Akiyama M, Takahashi A, Matoba N, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, Kubo M, Okada Y, Kamatani Y
    • Journal Title

      Nature Genetics

      Volume: 50 Pages: 390-400

    • DOI

      10.1038/s41588-018-0047-6

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Decrease in PSCA expression caused by helicobacter pylori infection may promote progression to severe gastritis2017

    • Author(s)
      Toyoshima O, Tanikawa C, Yamamoto R, Watanabe H, Yamashita H, Sakitani K, Yoshida S, Kubo M, Matsuo K, Ito H, Koike K, Seto Y, Matsuda K.
    • Journal Title

      Oncotarget

      Volume: 9 Issue: 3 Pages: 3936-3945

    • DOI

      10.18632/oncotarget.23278

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a p53-repressed gene module in breast cancer cells2017

    • Author(s)
      Miyamoto T, Tanikawa C, Yodsurang V, Zhang YZ, Imoto S, Yamaguchi R, Miyano S, Nakagawa H, Matsuda K
    • Journal Title

      Oncotarget

      Volume: 8(34) Pages: 55821-55836

    • DOI

      10.18632/oncotarget.19608

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Identification of a novel p53 target, COL17A1, that inhibits breast cancer cell migration and invasion2017

    • Author(s)
      Yodsurang Varalee、Tanikawa Chizu、Miyamoto Takafumi、Lo Paulisally Hau Yi、Hirata Makoto、Matsuda Koichi
    • Journal Title

      Oncotarget

      Volume: 8 Pages: 55790-55803

    • DOI

      10.18632/oncotarget.18433

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Genome-wide association study identifies 112 new loci for body mass index in the Japanese population.2017

    • Author(s)
      Akiyama M, Okada Y, Kanai M, Takahashi A, Momozawa Y, Ikeda M, Iwata N, Ikegawa S, Hirata M, Matsuda K, Iwasaki M, Yamaji T, Sawada N, Hachiya T, Tanno K, Shimizu A, Hozawa A, Minegishi N, Tsugane S, Yamamoto M, Kubo M and Kamatani Y
    • Journal Title

      Nature Genetics

      Volume: 49 Pages: 1458-1462

    • DOI

      10.1038/ng.3951

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Identification of a p53 target, CD137L, that mediates growth suppression and immune response of osteosarcoma cells2017

    • Author(s)
      Yusuke Tsuda, Chizu Tanikawa, Takafumi Miyamoto, Makoto Hirata, Varalee Yodsurang, Yao-zhong Zhang, Seiya Imoto, Rui Yamaguchi, Satoru Miyano, Hiroshi Takayanagi, Hirotaka Kawano, Hidewaki Nakagawa, Sakae Tanaka, and Koichi Matsuda
    • Journal Title

      Scientific Reports

      Volume: 7(1) Pages: 10739-10739

    • DOI

      10.1038/s41598-017-11208-x

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Regulation of tubular recycling endosome biogenesis by the p53-MICALL1 pathway2017

    • Author(s)
      Takahashi Yukie、Tanikawa Chizu、Miyamoto Takafumi、Hirata Makoto、Wang Guanxiong、Ueda Koji、Komatsu Tsunehiko、Matsuda Koichi
    • Journal Title

      Int J Oncol.

      Volume: 51 Pages: 724-736

    • DOI

      10.3892/ijo.2017.4060

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Argininosuccinate synthase 1 is an intrinsic Akt repressor transactivated by p532017

    • Author(s)
      Miyamoto Takafumi、Lo Paulisally Hau Yi、Saichi Naomi、Ueda Koji、Hirata Makoto、Tanikawa Chizu、Matsuda Koichi
    • Journal Title

      Sci Adv

      Volume: 3 Pages: 1603204-1603204

    • DOI

      10.1126/sciadv.1603204

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] The Transcriptional Landscape of p53 Signalling Pathway2017

    • Author(s)
      Tanikawa C, Zhang YZ, Yamamoto R, Tsuda Y, Tanaka M, Funauchi Y, Mori J, Imoto S, Yamaguchi R, Nakamura Y, Miyano S, Nakagawa H, Matsuda K
    • Journal Title

      EBioMedicine

      Volume: 20 Pages: 109-119

    • DOI

      10.1016/j.ebiom.2017.05.017

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Meta-analysis identifies five novel loci associated with endometriosis highlighting key genes involved in hormone metabolism2017

    • Author(s)
      Sapkota Y, Steinthorsdottir V, Morris AP, et al.
    • Journal Title

      Nature Communications

      Volume: 8 Pages: 15539-15539

    • DOI

      10.1038/ncomms15539

    • Related Report
      2017 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] EPSIN 3, A Novel p53 Target, Regulates the Apoptotic Pathway and Gastric Carcinogenesis2017

    • Author(s)
      Mori J, Tanikawa C, Ohnishi N, Funauchi Y, Toyoshima O, Ueda K, Matsuda K.
    • Journal Title

      Neoplasia.

      Volume: 19 Pages: 185-195

    • DOI

      10.1016/j.neo.2016.12.010

    • Related Report
      2017 Annual Research Report 2016 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Overview of BioBank Japan follow-up data in 32 diseases2017

    • Author(s)
      Hirata M, Nagai A, Kamatani Y, Ninomiya T, Tamakoshi A, Yamagata Z, Kubo M, Muto K, Kiyohara Y, Mushiroda T, Murakami Y, Yuji K, Furukawa Y, Zembutsu H, Tanaka T, Ohnishi Y, Nakamura Y; BioBank Japan Cooperative Hospital Group., Matsuda K.
    • Journal Title

      Journal of Epidemiology

      Volume: 27 Issue: Supplement_III Pages: S22-S28

    • DOI

      10.1016/j.je.2016.12.006

    • NAID

      130006832563

    • ISSN
      0917-5040, 1349-9092
    • Related Report
      2016 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Cross-sectional analysis of BioBank Japan clinical data: A large cohort of 200,000 patients with 47 common diseases2017

    • Author(s)
      Hirata M, Kamatani Y, Nagai A, Kiyohara Y, Ninomiya T, Tamakoshi A, Yamagata Z, Kubo M, Muto K, Mushiroda T, Murakami Y, Yuji K, Furukawa Y, Zembutsu H, Tanaka T, Ohnishi Y, Nakamura Y; BioBank Japan Cooperative Hospital Group., Matsuda K.
    • Journal Title

      Journal of Epidemiology

      Volume: 27 Issue: Supplement_III Pages: S9-S21

    • DOI

      10.1016/j.je.2016.12.003

    • NAID

      130006832556

    • ISSN
      0917-5040, 1349-9092
    • Related Report
      2016 Annual Research Report
  • [Journal Article] Regulation of myo-inositol biosynthesis by p53-ISYNA1 pathway.2016

    • Author(s)
      Tomoyuki Koguchi, Chizu Tanikawa, Jinichi Mori, Yoshiyuki Kojima, Koichi Matsuda
    • Journal Title

      Int J Oncol.

      Volume: 印刷中 Pages: 2415-24

    • DOI

      10.3892/ijo.2016.3456

    • Related Report
      2016 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Presentation] Multi-Omics analysis of tumor suppressor p53 signaling pathway2018

    • Author(s)
      Koichi Matsuda
    • Organizer
      Program IARI symposium CRCL
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Cancer susceptible germline variants and their applications for precision medicine2017

    • Author(s)
      Koichi Matsuda
    • Organizer
      The 1st International Conference for Precision Cancer Medicine(ICPC2017)
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research / Invited
  • [Presentation] Identification of p53 downstream pathway by multiomics analysis2017

    • Author(s)
      Koichi Matsuda,Chizu Tanikawa
    • Organizer
      17th International p53 Workshop
    • Related Report
      2017 Annual Research Report
    • Int'l Joint Research
  • [Presentation] がんのゲノム医療実現に向けて:ゲノム解析による 疾患発症メカニズムの解明と 個別化医療2017

    • Author(s)
      Koichi Matsuda
    • Organizer
      第14回 Tokyo Metropolitan Kidney Cancer Meeting
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] From cancer etiology by molecular epidemiological techniques to cancer prevention research2017

    • Author(s)
      Koichi Matsuda
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
    • Invited
  • [Presentation] Identification of a p53-repressed gene module in breast cancer cells2017

    • Author(s)
      Takafumi Miyamoto , Chizu Tanikawa , Seiya Imoto , Rui Yamaguchi , Satoru Miyano , Hidewaki Nakagawa5 , Koichi Matsuda
    • Organizer
      第76会日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Identification of a novel p53 target, COL17A1, that inhibits breast cancer cell migration and invasion2017

    • Author(s)
      Varalee Yodsurang , Chizu Tanikawa , Makoto Hirata , Takafumi Miyamoto , Yao-zhong Zhang , Satoru Miyano , Seiya Imoto , Rui Yamaguchi , Hidewaki Nakagawa , Yusuke Nakamura , Koichi Matsuda
    • Organizer
      第76会日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] The transcriptional landscape of p53 signalling pathway2017

    • Author(s)
      Chizu Tanikawa , Yao-zhong Zhang , Seiya Imoto , Rui Yamaguchi , Yusuke Nakamura , Satoru Miyano , Hidewaki Nakagawa , Koichi Matsuda
    • Organizer
      第76会日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Establishment of BioBank Japan searching system for biospecimen, based on clinical information database2017

    • Author(s)
      Makoto Hirata , Seiya Imoto , Yoichi Furukawa , Yoshinori Murakami , Koichi Matsuda
    • Organizer
      第76会日本癌学会学術総会
    • Related Report
      2017 Annual Research Report
  • [Presentation] Current progress in cancer genomics and genetics2016

    • Author(s)
      Koichi Matsuda
    • Organizer
      The 75th Annual meeting of the Japanese cancer association
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Related Report
      2016 Annual Research Report
    • Invited
  • [Presentation] 次世代DNAシークエンスによるがんの個別化医療の可能性2016

    • Author(s)
      松田浩一
    • Organizer
      癌治療学会
    • Place of Presentation
      パシフィコ横浜(神奈川県・横浜市)
    • Related Report
      2016 Annual Research Report
    • Invited

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Published: 2016-04-26   Modified: 2018-12-17  

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