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The role of reactive sulfur species and cysteinyl-tRNA synthetase2 in lung cancer

Research Project

Project/Area Number 19K21266
Project/Area Number (Other) 18H06155 (2018)
Research Category

Grant-in-Aid for Research Activity Start-up

Allocation TypeMulti-year Fund (2019)
Single-year Grants (2018)
Review Section 0901:Oncology and related fields
Research InstitutionTohoku University

Principal Investigator

Tsukita Yoko  東北大学, 大学病院, 医員 (50822566)

Project Period (FY) 2018-08-24 – 2020-03-31
Project Status Completed (Fiscal Year 2019)
Budget Amount *help
¥2,730,000 (Direct Cost: ¥2,100,000、Indirect Cost: ¥630,000)
Fiscal Year 2019: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2018: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Keywords肺癌 / CARS2
Outline of Research at the Start

近年、活性イオウ分子種の一種であるシステインパースルフィド(Csy-SSH)とその合成酵素であるシステイニルtRNA 合成酵素(cysteinyl-tRNA synthetase:CARS)2 が発見された。システインパースルフィドは活性酸素種(ROS)の強力な消去剤であると同時に、癌においては予後不良因子として知られるdynamin-related protein(Drp)1 を不活性化することが報告されている。CARS2 の癌における役割は未知であり、本研究ではヒト肺癌検体と肺癌細胞株を用いて肺癌におけるCARS2の役割を明らかにする。

Outline of Final Research Achievements

Cysteinyl-tRNA synthetase (CARS)2 is known as a novel cysteine hydropersulfide synthase. In our lung cancer tissue biobank, CARS2 mRNA expression decreased in cancer tissues compared to normal tissues. The protein expression of CARS2 in relapsed cancers tended to be lower than in non-relapsed cancers. CARS2 expression significantly correlated with expression of genes encoding other enzymes involved in sulfur metabolism.
These data suggest that sulfur metabolis is associated with the carcinogenesis and cancers vary in their dependence on sulfur metabolism.

Academic Significance and Societal Importance of the Research Achievements

CARS2が肺癌における発癌・悪性度に寄与している可能性を示した。肺癌におけるCARS2を含むイオウ代謝の関与を明らかにすることは、肺癌の発生や進展に関する未知のメカニズムの解明につながる。さらには、現在の薬物療法の主体である殺細胞性抗がん剤、分子標的治療、免疫療法とは異なる治療標的の発見につながる可能性を秘めている。

Report

(3 results)
  • 2019 Annual Research Report   Final Research Report ( PDF )
  • 2018 Annual Research Report
  • Research Products

    (4 results)

All 2019 2018

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

  • [Journal Article] Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas2019

    • Author(s)
      Tsukita Yoko、Fujino Naoya、Miyauchi Eisaku、Saito Ryoko、Fujishima Fumiyoshi、Itakura Koji、Kyogoku Yorihiko、Okutomo Koji、Yamada Mitsuhiro、Okazaki Tatsuma、Sugiura Hisatoshi、Inoue Akira、Okada Yoshinori、Ichinose Masakazu
    • Journal Title

      Molecular Cancer

      Volume: 18 Issue: 1 Pages: 24-24

    • DOI

      10.1186/s12943-019-0953-y

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor52018

    • Author(s)
      Yoko Tsukita, Tatsuma Okazaki, Satoru Ebihara, Riyo Komatsu, Mayumi Nihei, Makoto Kobayashi, Taizou Hirano, Hisatoshi Sugiura, Tsutomu Tamada, Nobuyuki Tanaka, Yasufumi Sato, Hideo Yagita, Masakazu Ichinose
    • Journal Title

      OncoImmunology.

      Volume: 8(2) Issue: 2 Pages: 1543526-1543526

    • DOI

      10.1080/2162402x.2018.1543526

    • Related Report
      2018 Annual Research Report
    • Peer Reviewed / Open Access
  • [Presentation] Axl Receptor Tyrosine Kinase Up-regulates Ligands for Programmed Cell Death 1 in Lung Adenocarcinoma2018

    • Author(s)
      Yoko Tsukita, Naoya Fujino, Eisaku Miyauchi, Koji Itakura, Yorihiko Kyogoku, Mitsuhiro Yamada, Tatsuma Okazaki, Hisatoshi Sugiura, Masakazu Ichinose
    • Organizer
      American Thoracic Society Conferance
    • Related Report
      2018 Annual Research Report
    • Int'l Joint Research
  • [Presentation] Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas2018

    • Author(s)
      Yoko Tsukita, Eisaku Miyauchi, Ryoko Saito, Tatsuma Okazaki, Akira Inoue, Yoshinori Okada, Masakazu Ichinose
    • Organizer
      日本癌学会学術総会
    • Related Report
      2018 Annual Research Report

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Published: 2018-08-27   Modified: 2024-03-26  

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