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Functional analysis of ERK-regulated genes responsible for onset/relapse of cancers

Research Project

Project/Area Number 17K08650
Research Category

Grant-in-Aid for Scientific Research (C)

Allocation TypeMulti-year Fund
Section一般
Research Field Pathological medical chemistry
Research InstitutionThe University of Tokyo

Principal Investigator

Kubota Yuji  東京大学, 医科学研究所, 助教 (70614973)

Project Period (FY) 2017-04-01 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2017: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Keywordsがん / MAPK経路 / ERK経路 / シグナル伝達 / 再発癌 / 抗癌剤抵抗性
Outline of Final Research Achievements

The ERK pathway (Raf-MEK-ERK) is activated by mitogenic stimuli and mediates proliferative and pro-survival signals. Somatic mutations in this pathway are frequently found in various cancers, and most of these oncogenes, such as EGFR, Ras and Raf, induce abnormal activation of ERK. However, the detailed molecular mechanism of the process by which they cause carcinogenesis. In this study, I performed global gene expression analysis of human cell-lines with high ERK activity and found that the oncogene-induced strong and constitutive ERK activation increases the expression of proteins and non-coding RNAs that promote carcinogenesis or acquired anticancer drug resistance.

Academic Significance and Societal Importance of the Research Achievements

ERK経路を構成する遺伝子の多くは様々な癌で高率に変異が認められる。その多くはERKシグナルを異常活性化して癌化や抗癌剤抵抗性を誘導するが、その分子的基盤は不明な点が多かった。本研究により、癌遺伝子に由来する強力なERKシグナル下流において、発癌および抗癌剤抵抗性の獲得に寄与する様々な遺伝子とその機能が明らかにされた。これらの知見は新たな分子標的や癌治療法の開発を促進すると期待される。

Report

(2 results)
  • 2019 Final Research Report ( PDF )
  • 2017 Research-status Report
  • Research Products

    (8 results)

All 2018 2017

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 1 results) Presentation (6 results) (of which Int'l Joint Research: 1 results)

  • [Journal Article] A guanine derivative as a new MEK inhibitor produced by Streptomyces sp. MK63-43F2.2018

    • Author(s)
      M. Iijima, Yuji Kubota, R. Sawa, Yumiko Kubota, M. Hatano, M. Igarashi, M. Kawada, I. Momose, M. Takekawa, M. Shibasaki.
    • Journal Title

      J. Antibiot.

      Volume: 71 Issue: 1 Pages: 135-138

    • DOI

      10.1038/ja.2017.100

    • Related Report
      2017 Research-status Report
    • Peer Reviewed
  • [Journal Article] WGA-based lectin affinity gel electrophoresis: A novel method for the detection of O-GlcNAc-modified proteins2017

    • Author(s)
      Kubota Yuji、Fujioka Ko、Takekawa Mutsuhiro
    • Journal Title

      PLOS ONE

      Volume: 12 Issue: 7 Pages: e0180714-e0180714

    • DOI

      10.1371/journal.pone.0180714

    • Related Report
      2017 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] 癌に由来するMEK遺伝子変異体の 異常リン酸化の機能解析および 病理学的意義の解明2018

    • Author(s)
      久保田裕二、木下栄司、武川睦寛
    • Organizer
      東京大学医科学研究所共同研究拠点事業 平成29年度成果報告会
    • Related Report
      2017 Research-status Report
  • [Presentation] フィードバック・リン酸化によるERKシグナル制御機構の数理シミュレーション解析2018

    • Author(s)
      久保田裕二、武川睦寛
    • Organizer
      第1回 MMDS、医科学研究所、新領域創成科学研究科合同ワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] A novel method for the detection of O-GlcNAc-modified proteins: WGA-based lectin affinity gel electrophoresis (WGA-SDS-PAGE)2017

    • Author(s)
      Yuji Kubota, Ko Fujioka and Mutsuhiro Takekawa
    • Organizer
      プロテイン・アイランド松山
    • Related Report
      2017 Research-status Report
    • Int'l Joint Research
  • [Presentation] 癌および先天性Ras/MAPK 症候群におけるMEK 変異体の異常活性化機構の解明と特異的阻害剤の同定2017

    • Author(s)
      久保田裕二、武川睦寛
    • Organizer
      新学術領域「数理シグナル」 第1回若手ワークショップ
    • Related Report
      2017 Research-status Report
  • [Presentation] Negative regulation of the ERK pathway by caspase-mediated cleavage of MEK1 during apoptosis.2017

    • Author(s)
      Yuji Kubota, Tomoyuki Tsuchiya and Mutsuhiro Takekawa
    • Organizer
      第76回 日本癌学会学術総会
    • Related Report
      2017 Research-status Report
  • [Presentation] WGA-based lectin affinity gel electrophoresis. A novel method for the detection of O-GlcNAc-modified proteins2017

    • Author(s)
      Yuji Kubota, Ko Fujioka and Mutsuhiro Takekawa
    • Organizer
      生命科学系学会合同年次大会(第40回 日本分子生学会、第90回 日本生化学会大会
    • Related Report
      2017 Research-status Report

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Published: 2017-04-28   Modified: 2023-01-30  

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