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

• Project/Area Number: 19K21266
• Project/Area Number (Other): 18H06155 (2018)
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund (2019); Single-year Grants (2018)
• Review Section: 0901:Oncology and related fields
• Research Institution: Tohoku 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: ¥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。

Research Products

• [Journal Article] Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas (2019)
  • 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
  • Peer Reviewed / Open Access
• [Journal Article] Beneficial effects of sunitinib on tumor microenvironment and immunotherapy targeting death receptor5 (2018)
  • 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
  • Peer Reviewed / Open Access
• [Presentation] Axl Receptor Tyrosine Kinase Up-regulates Ligands for Programmed Cell Death 1 in Lung Adenocarcinoma (2018)
  • 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
  • Int'l Joint Research
• [Presentation] Axl kinase drives immune checkpoint and chemokine signalling pathways in lung adenocarcinomas (2018)
  • 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