A study for molecular mechanism of the Cdk-Pin1 axis in cancer stem cell

• Project/Area Number: 25830087
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Tumor biology
• Research Institution: Yokohama City University
• Principal Investigator: NISHI Mayuko 横浜市立大学, 医学(系)研究科(研究院), 特任助教 (90635343)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Project Status: Completed (Fiscal Year 2014)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2013: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 癌幹細胞 / リン酸化 / 癌抑制遺伝子 / 細胞老化

Outline of Final Research Achievements

We recently established an induced cancer stem cell (CSC)-like model. We utilized the cell model for drug screening to inhibit the Cdk-Pin1 axis in CSCs. Withaferin A (WA) was identified as a compound inhibiting Cdk activity by inducing p21. WA inhibited not only the stemness and self-renewal properties of CSCs but also their ability of migration and invasion. WA decreased both the tumor initiation and the tumor-forming ability of CSCs in an immunosuppressed mouse model. We further attempted to identify functional Cdk substarates by a protomic approach using Pin1 as a molecular probe. We indentified several target proteins for further analysis.

Research Products

• [Journal Article] Development of an induced cancer stem cell model for drug discovery. (2015)
  • Author(s): Nishi M, Ryo A.
  • Journal Title: Cancer Cell & Microenvironment Volume: 1:e461
  • DOI: 10.14800/ccm.461
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] Induced cancer stem-like cells as a model for biological screening and discovery of agents targeting phenotypic traits of cancer stem cell. (2014)
  • Author(s): Nishi M, Akutsu H, Kudoh A, Kimura H, Yamamoto N, Umezawa A, Lee SW, Ryo A.
  • Journal Title: Oncotarget Volume: 5(18) Pages: 8665-8680
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Presentation] In vitro generation of cells with cancer stem-cell properties from human prostate epithelial cells (2013)
  • Author(s): Mayuko Nishi, Yukiko Watanabe, Akihide Ryo
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜（神奈川県横浜市）
• [Presentation] Induction of cells with cancer stem cell properties from p53-deficient somatic cells (2013)
  • Author(s): Mayuko Nishi, Akihide Ryo
  • Organizer: 2013 American Association for Cancer Research Meeting, Molecular Targets and Cancer Therapeutics
  • Place of Presentation: Hynes Convention Center Boston, MA, USA.
• [Remarks] 横浜市立大学大学院医学研究科 微生物学・分子生体防御学
  • URL: https://www-user.yokohama-cu.ac.jp/~saikin/