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Identification of cancer initiating cell factors and an attempt of drug development

Research Project

Project/Area Number 26670625
Research Category

Grant-in-Aid for Challenging Exploratory Research

Allocation TypeMulti-year Fund
Research Field Respiratory surgery
Research InstitutionNagoya University

Principal Investigator

SUZUKI Motoshi  名古屋大学, 医学(系)研究科(研究院), 講師 (80236017)

Co-Investigator(Kenkyū-buntansha) FUKUI Takayuki  名古屋大学, 医学部附属病院, 病院講師 (70463198)
WAKAHARA Keiko  名古屋大学, 医学部附属病院, 病院講師 (00631433)
KATO Sei-ichi  名古屋大学, 大学院医学系研究科, 講師 (30584669)
Nishida Atsushi  千葉大学, 大学院薬学研究院, 教授 (80130029)
Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,640,000 (Direct Cost: ¥2,800,000、Indirect Cost: ¥840,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Keywords肺がん / がん幹細胞 / 低分子化合物 / 肺癌 / 抗癌剤 / 分子標的治療薬
Outline of Final Research Achievements

We collected clinical lung cancer specimens and transplanted each of in the immune-deficient mice. Xenografts were recovered after tumor formation, collagenase-treated, and sorted for CD166 positive population. In a cell line, the CD166 positive cells successfully formed secondary tumors in mice. We performed database analysis to figure out a gene candidate which may contribute to the cancer initiating cell nature. By using the above cell line, we established a stable cell line that is associated with a knockdown of this gene, and inoculated thousands of cells in mice. Results are forthcoming. We also screened for an inhibitor against this gene product. Among the 2000 candidates, we found a compound that inhibits the activity. To decrease the EC50 value, we started optimization of this compound.

Report

(3 results)
  • 2015 Annual Research Report   Final Research Report ( PDF )
  • 2014 Research-status Report
  • Research Products

    (16 results)

All 2016 2015 2014

All Journal Article (12 results) (of which Peer Reviewed: 12 results,  Acknowledgement Compliant: 5 results,  Open Access: 3 results) Presentation (4 results) (of which Invited: 2 results)

  • [Journal Article] Effect of pH on the misincorporation rate of DNA polymerase eta2016

    • Author(s)
      Nishimoto N, Suzuki M, Izuta S
    • Journal Title

      Biol Pharm Bull

      Volume: in press

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Resveratrol-induced transcriptional up-regulation of ASMase (SMPD1) of human leukemia and cancer cells.2016

    • Author(s)
      Mizutani N, Omori Y, Kawamoto Y, Sobue S, Ichihara M, Suzuki M, Kyogashima M, Nakamura M, Tamiya-Koizumi K, Nozawa Y, Murate T.
    • Journal Title

      Biochem Biophys Res Commun

      Volume: 470 Issue: 4 Pages: 851-856

    • DOI

      10.1016/j.bbrc.2016.01.134

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] ROR1 sustains caveolae and survival signaling as a scaffold of cavin-1 and caveolin-12016

    • Author(s)
      Yamaguchi T, Lu C, Yanagisawa K, Can Lu, Usukura J, Cheng J, Hotta N, Shimada Y, Ida R, Isomura H, Suzuki M, Fujimoto T, Takahashi T
    • Journal Title

      Nat Commun

      Volume: 7 Issue: 1 Pages: 10060-10060

    • DOI

      10.1038/ncomms10060

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Targeting ceramide synthase 6-dependent metastasis-prone phenotype in lung cancer cells.2016

    • Author(s)
      Suzuki M, et al.
    • Journal Title

      J. Clin. Invest.

      Volume: 126 Issue: 1 Pages: 254-265

    • DOI

      10.1172/jci79775

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Receptor tyrosine kinase-like orphan receptor 1, a target of NKX2-1/TTF-1 lineage-survival oncogene, inhibits apoptosis signal-regulating kinase 1-mediated pro-apoptotic signaling in lung adenocarcinoma2016

    • Author(s)
      Ida L, Yamaguchi T, Yanagisawa K, Kajino T, Shimada Y, Suzuki M, Takahashi T
    • Journal Title

      Cancer Sci

      Volume: 107 Issue: 2 Pages: 155-161

    • DOI

      10.1111/cas.12858

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Increased Acid Ceramidase Expression depends on Upregulation of Androgen-dependent Deubiquitinases, USP2, in a Human Prostate Cancer Cell Line, LNCaP.2015

    • Author(s)
      Naoki Mizutani, Minami Inoue, Yukari Omori, Hiromi Ito, Keiko Tamiya-Koizumi, Akira Takagi, Tetsuhito Kojima, Mitsuhiro Nakamura, Soichiro Iwaki, Masahiro Nakatochi, Motoshi Suzuki, Yoshinori Nozawa, Takashi Murate
    • Journal Title

      J. Biochem.

      Volume: 印刷中 Issue: 4 Pages: 309-319

    • DOI

      10.1093/jb/mvv039

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] miR-342-3p regulates MYC transcriptional activity via direct repression of E2F1 in human lung cancer.2015

    • Author(s)
      Tai MC, Kajino T, Nakatochi M, Arima C, Shimada Y, Suzuki M, Miyoshi H, Yatabe Y, Yanagisawa K, Takahashi T.
    • Journal Title

      Carcinogenesis

      Volume: 36 Pages: 1464-1473

    • DOI

      10.1093/carcin/bgv152

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Increased SPHK2 transcription of human colon cancer cells in serum-depleted culture: the involvement of CREB transcription factor.2015

    • Author(s)
      Mizutani N, Omori Y, Tanaka K, Ito H, Takagi A, Kojima T, Nakatochi M, Ogiso H, Kawamoto Y, Nakamura M, Suzuki M, Kyogashima M, Koizumi K, Nozawa Y, Murate T.
    • Journal Title

      J Cell Biochem

      Volume: 116 Issue: 10 Pages: 2227-2238

    • DOI

      10.1002/jcb.25173

    • Related Report
      2015 Annual Research Report 2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Increased Acid Ceramidase Expression depends on Upregulation of Androgen-dependent Deubiquitinases, USP2, in a Human Prostate Cancer Cell Line, LNCaP2015

    • Author(s)
      Mizutani N, Inoue M, Omori Y, Ito H, Tamiya-Koizumi K, Takagi A, Kojima T, Nakamura M, Iwaki S, Nakatochi M, Suzuki M, Nozawa Y, and Murate M
    • Journal Title

      J Biochem

      Volume: in press

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Phosphorylated Sp1 is the regulator of DNA-PKcs and DNA ligase IV transcription of daunorubicin-resistant leukemia cell lines.2014

    • Author(s)
      Nishida Y, Mizutani N, Inoue M, Omori Y, Tamiya-Koizumi K, Takagi A, Kojima T, Suzuki M, Nozawa Y, Minami Y, Ohnishi K, Naoe T, Murate T.
    • Journal Title

      Biochim Biophys Acta.

      Volume: 1839 Issue: 4 Pages: 265-274

    • DOI

      10.1016/j.bbagrm.2014.02.004

    • Related Report
      2014 Research-status Report
    • Peer Reviewed
  • [Journal Article] Downregulation of POLD4 in Calu6 cells results in G1-S blockage through suppression of the Akt-Skp2-p27 pathway2014

    • Author(s)
      Huang Q, Suzuki M, Zeng Y, Zhang H, Yang D, Lin H
    • Journal Title

      Bioorg Med Chem Lett

      Volume: 24 Issue: 7 Pages: 1780-1783

    • DOI

      10.1016/j.bmcl.2014.02.033

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Lung adenocarcinoma subtypes definable by lung development-related miRNA expression profiles in association with clinicopathologic features2014

    • Author(s)
      Arima C, Kajino T, Tamada Y, Imoto S, ShimadaY, Nakatochi, M, Suzuki M, Isomura H, Yatabe Y, Yamaguchi T, Yanagisawa K, Miyano S, Takahashi T
    • Journal Title

      Carcinogenesis

      Volume: 35 Issue: 10 Pages: 2224-2231

    • DOI

      10.1093/carcin/bgu127

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] 1.Targeting CERS6-dependent Sphingolipid Pathway in Lung Cancer Cells2015

    • Author(s)
      Motoshi Suzuki, Takashi Murate, Mamoru Kyogashima and Takashi Takahashi
    • Organizer
      第74回日本癌学会総会
    • Place of Presentation
      愛知県名古屋市名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] セラミド合成酵素CerS6 の肺癌における役割とそれを利用した治療法の開発2015

    • Author(s)
      鈴木元
    • Organizer
      国際高等研究所研究プロジェクト「分子基盤に基づく生体機能への揺らぎとダイナミックネットワークの解明」
    • Place of Presentation
      京都府木津川市国際高等研究所
    • Year and Date
      2015-03-17
    • Related Report
      2014 Research-status Report
    • Invited
  • [Presentation] A pivotal role of CERS6 on the sphingolipid metabolic pathways and tumor metastasis in lung cancer.2014

    • Author(s)
      Suzuki M, Murate T, Kyogashima M and Takahashi T
    • Organizer
      第73回日本癌学会学術総会
    • Place of Presentation
      神奈川県横浜市パシフィコ横浜
    • Year and Date
      2014-09-27
    • Related Report
      2014 Research-status Report
  • [Presentation] 悪性腫瘍におけるスフィンゴ脂質代謝の果たす役割2014

    • Author(s)
      鈴木元
    • Organizer
      第15回Pharmaco-Hematologyシンポジウム
    • Place of Presentation
      愛知県名古屋市名古屋市立大学
    • Year and Date
      2014-05-23
    • Related Report
      2014 Research-status Report
    • Invited

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Published: 2014-04-04   Modified: 2017-05-10  

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