Targeting of mitochondrial NEET for treatment of osteosarcoma
Project/Area Number |
18K16671
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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) |
2018-04-01 – 2021-03-31
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Project Status |
Completed (Fiscal Year 2020)
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Budget Amount *help |
¥4,030,000 (Direct Cost: ¥3,100,000、Indirect Cost: ¥930,000)
Fiscal Year 2019: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2018: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
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Keywords | ミトコンドリア / ミトコンドリア小胞体係留分子 / 骨肉腫 / ミトコンドリア係留因子 / PDZD8 / ミトコンドリア酸化ストレス / 細胞死 / MAM / 胃癌 / がん化 / 前がん病変 / エネルギー代謝 / 酸化ストレス / ミトコンドリア結合分子 / プテロスチルベン / テザリング分子 / 酸化的リン酸化 |
Outline of Final Research Achievements |
Cancer stem cells undergo mitochondrial-dominant metabolism and produce ATP while maintaining an optimal ROS level. We then suspect that mitochondria might posess a unique regulatory mechanism for that purpose. We focused on PDZD8, which is one of the endoplasmic reticulum-mitochondrial tethering molecules as a mitochondrial control mechanism. PDZD8 showed cancer-specific expression, and its knockdown showed disappearance of suppression of oxygen consumption, increased oxidative stress, increased cytotoxicity, and decreased stemness in stress conditions. These results suggest that the endoplasmic reticulum-mediated control system of mitochondrial ROS-ATP balance is involved in the metabolic phenotype of cancer stem cells, suggesting that PDZD8 is a new therapeutic target for cancer stem cells.
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Academic Significance and Societal Importance of the Research Achievements |
がんにおける代謝の重要性は近年とくに注目されている。しかし、がんエネルギー代謝におけるミトコンドリア―小胞体係留分子に着目した研究はいまだに乏しい。本研究では、ミトコンドリア―小胞体係留分子であるミトコンドリアNEETおよびPDZD8のがん細胞における役割を解明し、これらを標的とする治療戦略に結びつく知見を得ることができた。とくに、骨肉腫のような治療的選択肢に乏しい悪性腫瘍に対する新規かつ有効な治療法の開発を可能にする知見が得られたことは、学術的にも社会的も大きな意義があったと考えられる。
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Report
(4 results)
Research Products
(38 results)
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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] 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
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Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Malic enzyme 1 is associated with tumor budding in oral squamous cell carcinomas.2020
Author(s)
Nakashima C, Kirita T, Yamamoto K, Mori S, Luo Y, Sasaki T, Fujii K, Ohmori H, Kawahara I, Mori T, Goto K, Kishi S, Fujiwara-Tani R, Kuniyasu H
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Journal Title
Int J Mol Sci
Volume: 21
Issue: 19
Pages: 7149-7149
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Clostridium perfringens enterotoxin induced claudin-4 to activate YAP in oral squamous cell carcinomas.2020
Author(s)
Nakashima C, Yamamoto K, Kishi S, Sasaki T, Ohmori H, Fujiwara-Tani R Mori S, Kawahara I, Nishiguchi Y, Mori T, Kondoh M, Luo Y, Kirita T, Kuniyasu H
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Journal Title
Oncotarget
Volume: 11
Issue: 4
Pages: 309-321
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Targeting claudin-4 enhances CDDP-chemosensitivity of gastric cancer2019
Author(s)
Nishiguchi Y, Fujiwara-Tani R, Sasaki T, Luo Y, Ohmori H, Kishi S, Mori S, Goto K, Yasui W, Sho M*, Kuniyasu H
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Journal Title
Oncotarget
Volume: 10
Issue: 22
Pages: 2189-2202
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Concurrent expression of CD47 and CD44 in colorectal cancer promotes malignancy2019
Author(s)
Fujiwara-Tani R, Sasaki T, Ohmori H, Luo Y, Goto K, Nishiguchi Y, Mori S, Nakashima C, Mori T, Miyagawa Y, Kawahara I, Fujii K, Kishi S, Tatsumoto N, Kuniyasu H
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Journal Title
Pathobiology
Volume: in press
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Magnetic hyperthermia using self-controlled heating elements consisting of Fe-Al milling alloy induces cancer cell apoptosis while preserving skeletal muscle.2019
Author(s)
Kawahara I, Goto K, Kodama K, Luo Y, Fujiwara-Tani R, Mori T, Miyagawa Y, Tanaka H, Kodama H, Hirayama A, Hosoito N, Taniguchi Y, Miki Y, Kuniyasu H
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Journal Title
Pathobiology
Volume: in press
Related Report
Peer Reviewed / Open Access
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[Journal Article] Intermittent calorie restriction enhances epithelial- mesenchymal transition through alteration of energy metabolism in a mouse tumor model.2018
Author(s)
Kusuoka O, Fujiwara-Tani R, Nakashima C, Fujii K, Ohmori H, Mori T, Kishi S, Miyagawa Y, Goto K, Kawahara I, Kuniyasu H
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Journal Title
Int J Oncol
Volume: 52
Pages: 413-423
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Expression of cytosolic malic enzyme (ME1) is associated with disease progression in human oral squamous cell carcinoma2018
Author(s)
Nakashima C, Yamamoto K, Fujiwara-Tani R, Luo Y, Matsushima S, Fujii K, Ohmori H, Sasahira T, Sasaki T, Kitadai Y, Kirita T, Kuniyasu H
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Journal Title
Cancer Sci
Volume: in press
Issue: 6
Pages: 2036-2045
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Pro-metastatic signaling of elaidic acid, a trans fatty acid, is associated with lipid rafts.2018
Author(s)
Kishi S, Fujiwara-Tani R, Luo Y, Kawahara I, Goto K, Fujii K, Ohmori H, Nakashima C, Sasaki T, Kuniyasu H
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Journal Title
Oncol Lett
Volume: 15
Pages: 4423-4426
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
Related Report
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