Molecular Mechanisms behind Cancer Cells-specific Oxygen Homeostasis and Their Influence on Tumor Radioresistance
| Project/Area Number |
26293276
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Partial Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Radiation science
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| Research Institution | Kyoto University |
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Principal Investigator |
Harada Hiroshi 京都大学, 放射線生物研究センター, 教授 (80362531)
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| Co-Investigator(Kenkyū-buntansha) |
吉村 通央 京都大学, 医学(系)研究科(研究院), 助教 (40597936)
小林 稔 京都大学, 医学(系)研究科(研究院), 研究員 (40644894)
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Project Status |
Completed (Fiscal Year 2016)
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| Budget Amount *help |
¥16,510,000 (Direct Cost: ¥12,700,000、Indirect Cost: ¥3,810,000)
Fiscal Year 2016: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000)
Fiscal Year 2015: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000)
Fiscal Year 2014: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
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| Keywords | 放射線治療 / がん / 治療抵抗性 / 酸素恒常性 / エネルギー代謝 / HIF-1 / 低酸素 / 微小環境 / 放射線治療抵抗性 / 低酸素応答 |
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| Outline of Final Research Achievements |
We identified IDH3, UCHL1, and LY6E as novel activators of HIF-1. IDH3 was found to induce tumor angiogenesis by stabilizing HIF-1A and upregulating HIF-1A TAD activity. UCHL1 was confirmed to promote distant tumor metastasis by deubiquitinating and stabilizing HIF-1A protein. LY6E was revealed to induce tumor angiogenesis by facilitating the transcriptional initiation of HIF-1A gene. The UCHL1-HIF-1 axis was found to induce radioresistance of cancer cells by increasing intracellular levels of an antioxidant, GSH, in a glucose-6-phosphate dehydrogenase-dependent pentose phosphate pathway (PPP)-dependent manner.
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Report
(4 results)
Research Products
(60 results)
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[Journal Article] Hypoxia-inducible factor 1 promotes chemoresistance of lung cancer by inducing carbonic anhydrase IX espression2017
Author(s)
Sowa T, Menju T, Chen-Yoshikawa TF, Takahashi K, Nishikawa S, Nakanishi T, Shikuma K, Motoyama H, Hijiya K, Aoyama A, Sato T, Sonobe M, Harada H, Date H
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Journal Title
Cancer Medicine
Volume: 6
Issue: 1
Pages: 288-297
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Evaluation of Tumor-associated Stroma and Its Relationship with Tumor Hypoxia Using Dynamic Contrast-enhanced CT and 18F Misonidazole PET in Murine Tumor Models.2016
Author(s)
Koyasu, S., Tsuji, Y., Harada, H., Nakamoto, Y., Nobashi, T., Kimura, H., Sano, K., Koizumi, K., Hamaji, M., Togashi, K.
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Journal Title
Radiology.
Volume: 278
Issue: 3
Pages: 734-41
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Midazolam inhibits the hypoxia-induced up-regulation of erythropoietin in the central nervous system2015
Author(s)
Matsuyama, T., Tanaka, T., Tatsumi, K., Daijo, H., Kai, S., Harada, H. and Fukuda, K.
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Journal Title
European Journal of Pharmacology
Volume: 761
Pages: 189-198
DOI
Related Report
Peer Reviewed
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[Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha2015
Author(s)
Goto Y, Zeng L, YeomCJ, Zhu Y, Morinibu A, Shinoyam K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H.
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Journal Title
Nat Commun
Volume: 6
Issue: 1
Pages: 1-10
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Aberrant IDH3α expression promotes malignant tumor growth by inducing HIF-1-mediated metabolic reprogramming and angiogenesis.2014
Author(s)
Zeng L, Morinibu A, Kobayashi M, Zhu Y, Wang X, Goto Y, Yeom CJ, Zhao T,Hirota K, Shinomiya K, Itasaka S, Yoshimura M, Guo G, Hammond EM, Hiraoka M, Harada H.
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Journal Title
Oncogene
Volume: epub
Issue: 36
Pages: 4758-4766
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Near-infraredfluorescence imaging of cancer mediated by tumor hypoxia and HIF1α/OATPs signaling axis.2014
Author(s)
Wu JB, Shao C, Li X, Shi C, Li Q, Hu P, Chen YT, Dou X, Sahu D, Li W, Harada H, Zhang Y, Wang R, Zhau HE, Chung LW.
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Journal Title
Biomaterials
Volume: 35
Issue: 28
Pages: 8175-8185
DOI
Related Report
Peer Reviewed
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