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The impact of JNK activity on the cancer stem cells

Research Project

Project/Area Number 26830065
Research Category

Grant-in-Aid for Young Scientists (B)

Allocation TypeMulti-year Fund
Research Field Tumor biology
Research InstitutionYamagata University

Principal Investigator

Okada Masashi  山形大学, 医学部, 講師 (70512614)

Project Period (FY) 2014-04-01 – 2016-03-31
Project Status Completed (Fiscal Year 2015)
Budget Amount *help
¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000)
Fiscal Year 2015: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2014: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
Keywordsがん幹細胞 / 腫瘍発生 / JNK / ROS / 薬剤抵抗性 / Kras / xenograft / 幹細胞性
Outline of Final Research Achievements

In this study, we demonstrated that JNK activity is necessary for maintenance of cancer stem cell (CSC) capacity on pancreatic CSCs as well as glioblastoma and lung CSCs in our previous reports. SP600125, a JNK inhibitor, treatment inhibits self-renewal and tumor-initiating capacity. Moreover, systemic administration of SP600125 reduces tumor-initiating CSCs in vivo. The SP600125 has been used in the overwhelming majority of studies, but the clinical safety profile is unknown. Therefore, we used a novel JNK inhibitor, AS602801 that has been developed for the treatment of inflammatory endometriosis. The AS602801 treatment also inhibits CSC capacity and tumor initiating capacity in vitro and in vivo. Generally chemoresistance associated with CSCs, we show that JNK is critically involved in the resistance of pancreatic CSCs to 5-FU and gemcitabine. The JNK inhibition promotes 5-FU or GEM-induced increase of intracellular reactive oxygen species.

Report

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

    (15 results)

All 2016 2015 2014

All Journal Article (12 results) (of which Int'l Joint Research: 7 results,  Peer Reviewed: 12 results,  Acknowledgement Compliant: 10 results,  Open Access: 5 results) Presentation (3 results)

  • [Journal Article] Time-staggered inhibition of JNK effectively sensitizes chemoresistant ovarian cancer cells to cisplatin and paclitaxel2016

    • Author(s)
      Seino M, Okada M, Sakaki H, Takeda H, Watarai H, Suzuki S, Seino S, Kuramoto K, Ohta T, Nagase S, Kurachi H, Kitanaka C
    • Journal Title

      Oncology Reports

      Volume: 35 Issue: 1 Pages: 593-601

    • DOI

      10.3892/or.2015.4377

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Reciprocal regulation of p53 and NF-κB by diacylglycerol kinase ζ.2016

    • Author(s)
      Tanaka T, Tsuchiya R, Hozumi Y, Nakano T, Okada M, Goto K.
    • Journal Title

      Adv Biol Regul.

      Volume: 60 Pages: 15-21

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] The novel JNK inhibitor AS602801 inhibits cancer stem cells in vitro and in vivo.2016

    • Author(s)
      Okada M, Kuramoto K, Takeda H, Watarai H, Sakaki H, Seino S, Seino M, Suzuki S, Kitanaka C.
    • Journal Title

      Oncotarget

      Volume: 19 Issue: 19 Pages: 27021-27032

    • DOI

      10.18632/oncotarget.8395

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] GSKJ4, A Selective Jumonji H3K27 Demethylase Inhibitor, Effectively Targets Ovarian Cancer Stem Cells.2015

    • Author(s)
      Sakaki H, Okada M, Kuramoto K, Takeda H, Watarai H, Suzuki S, Seino S, Seino M, Ohta T, Nagase S, Kurachi H, Kitanaka C.
    • Journal Title

      Anticancer Res.

      Volume: 12 Pages: 6607-14

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Differential contribution of ROS to resveratrol-induced cell death and loss of self-renewal capacity of ovarian cancer stem cells.2015

    • Author(s)
      Seino M, Okada M, Shibuya K, Seino S, Suzuki S, Takeda H, Ohta T, Kurachi H, Kitanaka C.
    • Journal Title

      Anticancer Res

      Volume: 1 Pages: 85-96

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Targeting the facilitative glucose transporter GLUT1 inhibits the self-renewal and tumor-initiating capacity of cancer stem cells.2015

    • Author(s)
      Shibuya K, Okada M, Suzuki S, Seino M, Seino S, Takeda H, Kitanaka C.
    • Journal Title

      Oncotarget

      Volume: 20 Issue: 2 Pages: 651-661

    • DOI

      10.18632/oncotarget.2892

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] JNK suppression of chemotherapeutic agents-induced ROS confers chemoresistance on pancreatic cancer stem cells.2015

    • Author(s)
      Suzuki S, Okada M, Shibuya K, Seino M, Sato A, Takeda H, Seino S, Yoshioka T, Kitanaka C.
    • Journal Title

      Oncotarget

      Volume: 1 Issue: 1 Pages: 458-470

    • DOI

      10.18632/oncotarget.2693

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
  • [Journal Article] Downregulation of diacylglycerol kinase zeta enhances activation of cytokine-induced NF-kB signaling pathway2014

    • Author(s)
      R. Tsuchiya, T. Tanaka, Y. Hozumi, T. Nakano, M. Okada, M. K. Topham, M. Iino, K. Goto
    • Journal Title

      BBA Molecular Cell Research

      Volume: 1853 Issue: 2 Pages: 361-369

    • DOI

      10.1016/j.bbamcr.2014.11.011

    • Related Report
      2015 Annual Research Report
    • Peer Reviewed
  • [Journal Article] Requirement of JNK signaling for self-renewal and tumor-initiating capacity of ovarian cancer stem cells.2014

    • Author(s)
      Seino M, Okada M, Shibuya K, Seino S, Suzuki S, Ohta T, Kurachi H, Kitanaka C.
    • Journal Title

      Anticancer Res.

      Volume: 9 Pages: 4723-4731

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Journal Article] Role of the N-terminal hydrophobic residues of DGKε in targeting the endoplasmic reticulum.2014

    • Author(s)
      Matsui H, Hozumi Y, Tanaka T, Okada M, Nakano T, Suzuki Y, Iseki K, Kakehata S, Topham MK, Goto K.
    • Journal Title

      Biochim Biophys Acta Molecular and Cell Biology of Lipids

      Volume: 1842 Issue: 10 Pages: 1440-1450

    • DOI

      10.1016/j.bbalip.2014.07.007

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Targeting the K-Ras--JNK axis eliminates cancer stem-like cells and prevents pancreatic tumor formation. Oncotarget.2014

    • Author(s)
      Okada M, Shibuya K, Sato A, Seino S, Suzuki S, Seino M, Kitanaka C.
    • Journal Title

      Oncotarget

      Volume: 13 Pages: 5100-5112

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Open Access / Acknowledgement Compliant
  • [Journal Article] Cellular expression and localization of DGKζ-interacting NAP1-like proteins in the brain and functional implications under hypoxic stress.2014

    • Author(s)
      Takahashi N, Hozumi Y, Tanaka T, Okada M, Iseki K, Hayasaka K, Goto K.
    • Journal Title

      Histochem Cell Biol

      Volume: 142 Issue: 5 Pages: 461-471

    • DOI

      10.1007/s00418-014-1226-x

    • Related Report
      2014 Research-status Report
    • Peer Reviewed / Acknowledgement Compliant
  • [Presentation] Targeting the K-Ras - JNK axis eliminates cancer stem-like cells and prevents pancreatic tumor formation2015

    • Author(s)
      Masashi Okada, Keita Shibuya, Atsushi Sato, Shuhei Suzuki, Manabu Seino and Chifumi Kitanaka
    • Organizer
      BMB2015
    • Place of Presentation
      神戸・ポートアイランド
    • Year and Date
      2015-12-01
    • Related Report
      2015 Annual Research Report
  • [Presentation] Targeting the K-Ras - JNK axis eliminates cancer stem-like cells and prevents pancreatic tumor formation2015

    • Author(s)
      Masashi Okada, Keita Shibuya, Atsushi Sato, Shuhei Suzuki, Manabu Seino, Chifumi Kitanaka
    • Organizer
      日本癌学会総会
    • Place of Presentation
      名古屋・名古屋国際会議場
    • Year and Date
      2015-10-08
    • Related Report
      2015 Annual Research Report
  • [Presentation] JNK contributes to temozolomide resistance of glioma stem cells via regulation of MGMT expression2014

    • Author(s)
      Masashi Okada, Atsushi Sato, Keita Shibuya, Shuhei Suzuki, Manabu Seino, Yoshitaka Narita, Soichiro Shibui, Takamasa Kayama, Chifumi Kitanaka
    • Organizer
      日本癌学会 年会
    • Place of Presentation
      パシフィコ横浜(神奈川県横浜市)
    • Year and Date
      2014-09-25 – 2014-09-27
    • Related Report
      2014 Research-status Report

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

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