Targeting of the mitochondria-ER-tethering protein PDZD8 for osteosarcoma treatment
Project/Area Number |
20K18007
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Research Category |
Grant-in-Aid for Early-Career Scientists
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Allocation Type | Multi-year Fund |
Review Section |
Basic Section 56020:Orthopedics-related
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Research Institution | Nara Medical University |
Principal Investigator |
Kishi Shingo 奈良県立医科大学, 医学部, 助教 (50790341)
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Project Period (FY) |
2020-04-01 – 2022-03-31
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Project Status |
Completed (Fiscal Year 2021)
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Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Fiscal Year 2020: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
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Keywords | ミトコンドリア繋留分子 / PDZD8 / 骨肉腫 / 活性酸素 / 鉄 / スニチニブ / プテロスチルベン / MAM / ミトコンドリア / 係留因子 / 酸化ストレス / 小胞体 / エネルギー代謝 |
Outline of Research at the Start |
PDZD8は最近報告された新規ミトコンドリア―小胞体間テザリング分子であるがその機能は明らかではない。申請者はこの分子の発現低下がミトコンドリア内の2価鉄を著増させATP合成酵素阻害剤に感受性となることを見出した。また、骨肉腫の臨床検体でこの分子の発現の亢進がみられた。以上からPDZD8を介したテザリングサイトはミトコンドリアの鉄代謝に深く関係し悪性腫瘍の代謝、生存に深く関係していることが考えられる。本分子のこのような機能は全く報告されていないものであり、関連シグナルや機能解析を行い治療標的化を目指す。
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Outline of Final Research Achievements |
Mitochondria-associated membranes (MAMs) have attracted much attention which tethers mitochondria and endoplasmic reticulum (ER) to influence substance transfer and metabolism between the two. In this study, we examined the function of PDZD8 among MAMs, suggesting that PDZD8 protein is expressed in a tumor-specific manner, regulating mitochondrial iron metabolism and suppressing ROS production. Inhibition of PDZD8 promoted the antitumor effects of anticancer drugs and pterostilbene, which inhibits F1F0-ATPase, from increased ROS production. Sunitinib might suppress PDZD8 as its off target.
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Academic Significance and Societal Importance of the Research Achievements |
PDZD8が腫瘍特異的に発現し、その抑制が抗がん剤などの抗腫瘍効果を促進したことは、PDZD8ががん治療における新たな分子標的となることが考えられる。とくに、SunitinibはPDZD8をoff targetとして抑制したことは、今後のPDZD8のシグナル経路の解明の手掛かりとなるとともに、PDZD8を標的とする創薬に繋がる知見と考えられる。
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Report
(3 results)
Research Products
(26 results)
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[Journal Article] Nutritional intervention for cancer sarcopenia.2021
Author(s)
Mori T, Kido A, Kawahara I, Nukaga S, Miyagawa Y, Goto K, Mori S, Kishi S, Fujii K, Fujiwara-Tani R, Kuniyasu H
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Journal Title
Ann Muscloskeletal Med
Volume: 5
Issue: 1
Pages: 001-004
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Role of Glycated High Mobility Group Box-1 in Gastric Cancer2021
Author(s)
Kishi Shingo、Nishiguchi Yukiko、Honoki Kanya、Mori Shiori、Fujiwara-Tani Rina、Sasaki Takamitsu、Fujii Kiyomu、Kawahara Isao、Goto Kei、Nakashima Chie、Kido Akira、Tanaka Yasuhito、Luo Yi、Kuniyasu Hiroki
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Journal Title
International Journal of Molecular Sciences
Volume: 22
Issue: 10
Pages: 5185-5185
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] BRAF Mutation Is Associated with Hyperplastic Polyp-Associated Gastric Cancer2021
Author(s)
Fujiwara-Tani Rina、Okamoto Ayaka、Katsuragawa Hiroyuki、Ohmori Hitoshi、Fujii Kiyomu、Mori Shiori、Kishi Shingo、Sasaki Takamitsu、Nakashima Chie、Kawahara Isao、Hojo Yudai、Nishiguchi Yukiko、Mori Takuya、Mizumoto Takeshi、Nagai Kenta、Luo Yi、Kuniyasu Hiroki
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Journal Title
International Journal of Molecular Sciences
Volume: 22
Issue: 23
Pages: 12724-12724
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Anti-stem cell property of pterostilbene in gastrointestinal cancer cells.2020
Author(s)
Mori S, Kishi S, Honoki K, Fujiwara-Tani R, Moriguchi T, Sasaki T, Fujii K, Tsukamoto S, Fujii H, Kido A, Tanaka Y, Luo Y, Kuniyasu H.
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Journal Title
Int J Mol Sci.
Volume: 21
Issue: 24
Pages: 9347-9347
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Effect of Proton Pump Inhibitors on Colorectal Cancer2020
Author(s)
Sasaki Takamitsu、Mori Shiori、Kishi Shingo、Fujiwara-Tani Rina、Ohmori Hitoshi、Nishiguchi Yukiko、Hojo Yudai、Kawahara Isao、Nakashima Chie、Fujii Kiyomu、Luo Yi、Kuniyasu Hiroki
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Journal Title
International Journal of Molecular Sciences
Volume: 21
Issue: 11
Pages: 3877-3877
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Role of Nuclear Claudin-4 in Renal Cell Carcinoma2020
Author(s)
Owari Takuya、Sasaki Takamitsu、Fujii Kiyomu、Fujiwara-Tani Rina、Kishi Shingo、Mori Shiori、Mori Takuya、Goto Kei、Kawahara Isao、Nakai Yasushi、Miyake Makito、Luo Yi、Tanaka Nobumichi、Kondoh Masuo、Fujimoto Kiyohide、Kuniyasu Hiroki
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Journal Title
International Journal of Molecular Sciences
Volume: 21
Issue: 21
Pages: 8340-8340
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Presentation] The creatine kinase is a metabolic vulnerability in Osteosarcoma.2020
Author(s)
Kishi S, Mori S, Fujiwara-Tani R, Hojo Y, Owar T, Mori T, Nukaga S, Kita M, Sasaki R, Honoki K, Kuniyasu H
Organizer
79th Annual Meeting of Japanese Association for Cancer, Hiroshima
Related Report
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