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2022 Fiscal Year Research-status Report

Osteosarcoma therapeutic strategy targeting anticancer drug resistance by mitochondrial transfer

Research Project

Project/Area Number 20K21659
Research InstitutionNara Medical University

Principal Investigator

國安 弘基  奈良県立医科大学, 医学部, 教授 (00253055)

Co-Investigator(Kenkyū-buntansha) 谷 里奈  奈良県立医科大学, 医学部, 講師 (20783872)
岸 真五  奈良県立医科大学, 医学部附属病院, 研究員 (50790341)
Project Period (FY) 2020-07-30 – 2024-03-31
Keywords薬剤耐性 / 幹細胞性 / ミトトランスファー / NFkBシグナル / HKGB1
Outline of Annual Research Achievements

昨年度の検討により、酸化型HMGB1がMSCのミトトランファー活性を高め、ミトトランスファーを受けたCRCの幹細胞性を高め、増殖促進、薬剤耐性を亢進させることが明らかになった。本年度は、酸化型HMGB1の細胞内シグナル経路を検討した。酸化型HMGB1はRAGEを受容体とし、NFkBシグナル経路を活性化した。NFkB阻害剤により酸化型HMGB1によるミトトランスファーは抑制され、NFkBがMSCにおけるミトトランスファーを誘導していることが明らかになった。さらに、ミトトランスファー実行タンパクであるMiro1のプロモーター領域には2か所にNFkBコンセンサスが存在し、ChIPアッセイによりこれらのコンセンサスがNFkBによるMiro1発現亢進に関与することが明らかになった。これらのことから、NFkB阻害剤を用いることでミトトランスファーによる薬剤耐性を解除することが可能であると考えられた。

Current Status of Research Progress
Current Status of Research Progress

2: Research has progressed on the whole more than it was originally planned.

Reason

計画通り、MSCからがん細胞へのミトトランスファーが癌細胞の幹細胞性を亢進させることで薬剤耐性を獲得させることを明らかにした。さらに、ミトトランスファーを誘導するリガンドとして酸化型HMGB1が関与すること、さらに、その細胞内シグナルとしてNFkBが関与することを明らかにした。これらのことから、ミトトランスファーを標的化する方策が示唆された。

Strategy for Future Research Activity

今後は、NFkB阻害剤を用いたミトトランスファーの阻害実験とがん細胞の幹細胞性を検討することにより、ミトトランスファー標的化ががん幹細胞の標的化につながることを解明して行く計画である。

Causes of Carryover

NFkB阻害剤による検討が2023年度に継続するため。

  • Research Products

    (19 results)

All 2023 2022 Other

All Int'l Joint Research (2 results) Journal Article (11 results) (of which Int'l Joint Research: 5 results,  Peer Reviewed: 11 results,  Open Access: 11 results) Presentation (5 results) (of which Int'l Joint Research: 4 results) Remarks (1 results)

  • [Int'l Joint Research] Nantong University(中国)

    • Country Name
      CHINA
    • Counterpart Institution
      Nantong University
  • [Int'l Joint Research] Saveetha Dental College(インド)

    • Country Name
      INDIA
    • Counterpart Institution
      Saveetha Dental College
  • [Journal Article] Claudin-4: A New Molecular Target for Epithelial Cancer Therapy2023

    • Author(s)
      Fujiwara-Tani Rina、Mori Shiori、Ogata Ruiko、Sasaki Rika、Ikemoto Ayaka、Kishi Shingo、Kondoh Masuo、Kuniyasu Hiroki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Pages: 5494~5494

    • DOI

      10.3390/ijms24065494

    • Peer Reviewed / Open Access
  • [Journal Article] Short Telomere Lesions with Dysplastic Metaplasia Histology May Represent Precancerous Lesions of Helicobacter pylori-Positive Gastric Mucosa2023

    • Author(s)
      Fujiwara-Tani Rina、Takagi Tadataka、Mori Shiori、Kishi Shingo、Nishiguchi Yukiko、Sasaki Takamitsu、Ikeda Masayuki、Nagai Kenta、Bhawal Ujjal Kumar、Ohmori Hitoshi、Fujii Kiyomu、Kuniyasu Hiroki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Pages: 3182~3182

    • DOI

      10.3390/ijms24043182

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] 5-Aminolevrinic Acid Exhibits Dual Effects on Stemness in Human Sarcoma Cell Lines under Dark Conditions2023

    • Author(s)
      Horii Shohei、Mori Shiori、Ogata Ruiko、Nukaga Shota、Nishida Ryoichi、Kishi Shingo、Sasaki Rika、Ikemoto Ayaka、Owari Takuya、Maesaka Fumisato、Honoki Kanya、Miyake Makito、Tanaka Yasuhito、Fujimoto Kiyohide、Fujiwara-Tani Rina、Kuniyasu Hiroki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Pages: 6189~6189

    • DOI

      10.3390/ijms24076189

    • Peer Reviewed / Open Access
  • [Journal Article] Berberine Induces Combined Cell Death in Gastrointestinal Cell Lines2023

    • Author(s)
      Mori Shiori、Fujiwara-Tani Rina、Gyoten Momoko、Nukaga Shota、Sasaki Rika、Ikemoto Ayaka、Ogata Ruiko、Kishi Shingo、Fujii Kiyomu、Kuniyasu Hiroki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Pages: 6588~6588

    • DOI

      10.3390/ijms24076588

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Lauric Acid Overcomes Hypoxia-Induced Gemcitabine Chemoresistance in Pancreatic Ductal Adenocarcinoma2023

    • Author(s)
      Takagi Tadataka、Fujiwara-Tani Rina、Mori Shiori、Kishi Shingo、Nishiguchi Yukiko、Sasaki Takamitsu、Ogata Ruiko、Ikemoto Ayaka、Sasaki Rika、Ohmori Hitoshi、Luo Yi、Bhawal Ujjal Kumar、Sho Masayuki、Kuniyasu Hiroki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 24 Pages: 7506~7506

    • DOI

      10.3390/ijms24087506

    • Peer Reviewed / Open Access
  • [Journal Article] Suppressive GLI2 fragment enhances liver metastasis in colorectal cancer2022

    • Author(s)
      Ogata Ruiko、Mori Shiori、Ohmori Hitoshi、Kishi Shingo、Fujiwara-Tani Rina、Sasaki Takamitsu、Nishiguchi Yukiko、Nakashima Chie、Goto Kei、Kawahara Isao、Luo Yi、Kuniyasu Hiroki
    • Journal Title

      Oncotarget

      Volume: 13 Pages: 122~135

    • DOI

      10.18632/oncotarget.28170

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Sunitinib and Pterostilbene Combination Treatment Exerts Antitumor Effects in Gastric Cancer via Suppression of PDZD82022

    • Author(s)
      Hojo Yudai、Kishi Shingo、Mori Shiori、Fujiwara-Tani Rina、Sasaki Takamitsu、Fujii Kiyomu、Nishiguchi Yukiko、Nakashima Chie、Luo Yi、Shinohara Hisashi、Kuniyasu Hiroki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Pages: 4002~4002

    • DOI

      10.3390/ijms23074002

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Journal Article] Gemcitabine Resistance in Pancreatic Ductal Carcinoma Cell Lines Stems from Reprogramming of Energy Metabolism2022

    • Author(s)
      Fujiwara-Tani Rina、Sasaki Takamitsu、Takagi Tadataka、Mori Shiori、Kishi Shingo、Nishiguchi Yukiko、Ohmori Hitoshi、Fujii Kiyomu、Kuniyasu Hiroki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Pages: 7824~7824

    • DOI

      10.3390/ijms23147824

    • Peer Reviewed / Open Access
  • [Journal Article] 5-Aminolevulinic acid overcomes hypoxia-induced radiation resistance by enhancing mitochondrial reactive oxygen species production in prostate cancer cells2022

    • Author(s)
      Owari Takuya、Tanaka Nobumichi、Nakai Yasushi、Miyake Makito、Anai Satoshi、Kishi Shingo、Mori Shiori、Fujiwara-Tani Rina、Hojo Yudai、Mori Takuya、Kuwada Masaomi、Fujii Tomomi、Hasegawa Masatoshi、Fujimoto Kiyohide、Kuniyasu Hiroki
    • Journal Title

      British Journal of Cancer

      Volume: 127 Pages: 350~363

    • DOI

      10.1038/s41416-022-01789-4

    • Peer Reviewed / Open Access
  • [Journal Article] Oxidized high mobility group B‐1 enhances metastability of colorectal cancer via modification of mesenchymal stem/stromal cells2022

    • Author(s)
      Kishi Shingo、Fujiwara‐Tani Rina、Honoki Kanya、Sasaki Rika、Mori Shiori、Ohmori Hitoshi、Sasaki Takamitsu、Miyagawa Yoshihiro、Kawahara Isao、Kido Akira、Tanaka Yasuhito、Kuniyasu Hiroki
    • Journal Title

      Cancer Science

      Volume: 113 Pages: 2904~2915

    • DOI

      10.1111/cas.15400

    • Peer Reviewed / Open Access
  • [Journal Article] An Axis between the Long Non-Coding RNA HOXA11-AS and NQOs Enhances Metastatic Ability in Oral Squamous Cell Carcinoma2022

    • Author(s)
      Nakashima Chie、Fujiwara-Tani Rina、Mori Shiori、Kishi Shingo、Ohmori Hitoshi、Fujii Kiyomu、Mori Takuya、Miyagawa Yoshihiro、Yamamoto Kazuhiko、Kirita Tadaaki、Luo Yi、Kuniyasu Hiroki
    • Journal Title

      International Journal of Molecular Sciences

      Volume: 23 Pages: 10704~10704

    • DOI

      10.3390/ijms231810704

    • Peer Reviewed / Open Access / Int'l Joint Research
  • [Presentation] Caprylic acid alleviates cachexia-induced myocardial damage by inhibiting HMGB1 via ketone body.2023

    • Author(s)
      Nukaga S, Rina Fujiwara-Tani R, Miyagawa Y, Kawahara I, Nishida R, Mori T, Goto K, Kishi S, Mori S, Fujii K, Ohmori H, Kuniyasu H
    • Organizer
      MASCC 2023 Annual Meeting, Nara, Japan, 2023.6.22-24
    • Int'l Joint Research
  • [Presentation] Safety assessment of modifying the blood-brain barrier by targeting claudin-5 in a cynomolgus monkey model.2023

    • Author(s)
      Kuzu T, Hashimoto Y, Wakayama E, Nishino I, Tachibana K, Okada Y, Hirayama R, Kuniyasu H, Kondoh M
    • Organizer
      Society of Toxicology (SOT) 62nd Annual Meeting and ToxExpo
    • Int'l Joint Research
  • [Presentation] Lauric acid enhances gemcitabine chemosensitivity by targeting hypoxia-induced mitochondrial dysfunction and stemness in pancreatic ductal adenocarcinoma.2023

    • Author(s)
      Takagi T, Fujiwara-Tani R, Mori S, Sho M, Kuniyasu H
    • Organizer
      American Association for Cancer Research Annual Meeting 2023
    • Int'l Joint Research
  • [Presentation] Pterostilbene enhances anticancer effect of lapatinib in gastric cancer cell lines.2023

    • Author(s)
      Nishiguchi Y, Rina Fujiwara-Tani, Shiori Mori, Sho M, Hiroki Kuniyasu
    • Organizer
      International Gastric Cancer Congress 2023, Yokohama, Japan, 2023.6.14-17
    • Int'l Joint Research
  • [Presentation] 酸化型HMGB1による間葉系幹細胞からのミトコンドリア移行は大腸癌細胞の薬剤耐性をもたらす2023

    • Author(s)
      佐々木里歌、岸真五、森汐莉、谷里奈、國安弘基
    • Organizer
      第112回日本病理学会総会
  • [Remarks] 奈良県立医科大学分子病理学講座

    • URL

      http://www.naramed-u.ac.jp/~molepath/

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Published: 2023-12-25  

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