Development of anti-cancer strategy by targeting tRNA modification enzymes

• Project/Area Number: 18K15241
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50010:Tumor biology-related
• Research Institution: Okayama University
• Principal Investigator: Fujimura Atsushi 岡山大学, 医歯薬学総合研究科, 助教 (10771082)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Project Status: Completed (Fiscal Year 2019)
• Budget Amount: ¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000); Fiscal Year 2019: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
• Keywords: がん幹細胞 / tRNA修飾酵素 / 翻訳メカニズム / 悪性脳腫瘍 / 微小環境 / tRNA修飾酵素群 / 癌の不均一性

Outline of Final Research Achievements

In this study, I focused on the molecular mechanism of "cancer stem cell-related translational manner." I revealed that tRNA modification enzyme X was crucial to sustain the stemness of glioma-initiating cells. I found that enzyme Y, which has similar structure and function of enzyme X, was also important for various kind of cancers. Moreover, I also identified enzyme Z as the other type of tRNA modification enzyme that controlled stemness in carcinoma. These findings prompt me to develop the anti-cancer strategy, especially next-generation anti-cancer drugs, which can target the cancer stem cells.

Academic Significance and Societal Importance of the Research Achievements

本研究で取り組んだ「tRNA修飾酵素群によるがんの翻訳制御機構」は、がん治療の妨げの元凶のひとつとされている「がん組織内の不均一性」を説明するための新しい試みである。今回明らかになったように、特定のtRNAにおける修飾核酸には、がんの進展を促進させたり、阻害させたりする機能があることが判明した。今回私が同定したtRNA修飾酵素群に対する阻害剤が開発できれば、これまで治療を困難にしてきたがん幹細胞を標的化することが可能な抗がん剤が開発される可能性があるという点で、重要な研究であると考える。

Research Products

• [Journal Article] Annexin A2-STAT3-Oncostatin M receptor axis drives phenotypic and mesenchymal changes in glioblastoma (2020)
  • Author(s): Matsumoto Y , Ichikawa T , Kurozumi K , Otani Y , Fujimura A , Fujii K , Tomita Y , Hattori Y , Uneda A , Tsuboi N , Kaneda K , Makino K , Date I
  • Journal Title: Acta Neuropathologica Communications Volume: ー Issue: 1 Pages: 42-42
  • DOI: 10.1186/s40478-020-00916-7
  • NAID: 120006840780
  • Peer Reviewed / Open Access
• [Journal Article] Intracranial Mesenchymal Chondrosarcoma Lacking the Typical Histopathological Features Diagnosed by <i>HEY1-NCOA2</i> Gene Fusion (2020)
  • Author(s): Uneda A, Kurozumi K, Fujimura A, Kamiya A, Hirose T, Yanai H, Date I.
  • Journal Title: NMC Case Report Journal Volume: 7 Issue: 2 Pages: 47-52
  • DOI: 10.2176/nmccrj.cr.2019-0123
  • NAID: 130007825982
  • ISSN: 2188-4226
  • Peer Reviewed / Open Access
• [Journal Article] 2-Methylthio Conversion of N6-Isopentenyladenosine in Mitochondrial tRNAs by CDK5RAP1 Promotes the Maintenance of Glioma-Initiating Cells (2019)
  • Author(s): Yamamoto Takahiro、Fujimura Atsushi、Wei Fan-Yan、Shinojima Naoki、Kuroda Jun-ichiro、Mukasa Akitake、Tomizawa Kazuhito
  • Journal Title: iScience Volume: 21 Pages: 42-56
  • DOI: 10.1016/j.isci.2019.10.012
  • NAID: 120006816645
  • Peer Reviewed / Open Access
• [Presentation] ミトコンドリアによる細胞障害性修飾核酸の解毒作用は悪性脳腫瘍幹細胞の維持に必須である (2020)
  • Author(s): （口頭発表）藤村篤史、山本隆広、魏范研、富澤一仁
  • Organizer: 第97回 日本生理学会（コロナ禍により、誌上開催）
• [Presentation] Defining the molecular characteristics of boron compounds proposes the concept of precision medicine in BNCT field (2018)
  • Author(s): Seiji Yasui, Atsushi Fujimura, Hiroyuki Michiue, Yasuaki Ichikawa, Shuichi Furuya, Mitsunobu Kano, Hideki Matsui
  • Organizer: ICNCT 18th
  • Int'l Joint Research
• [Patent(Industrial Property Rights)] ホウ素中性子捕捉療法の効果を最適化するがん病巣組織評価 (2018)
  • Inventor(s): 藤村篤史、松井秀樹
  • Industrial Property Rights Holder: 藤村篤史、松井秀樹
  • Industrial Property Rights Type: 特許
  • Filing Date: 2018
  • Overseas