Studies on the role of XBP1 in tumor malignancy
| Project/Area Number |
20611016
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Chemical biology
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| Research Institution | Keio University |
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Principal Investigator |
TASHIRO Etsu Keio University, 理工学部, 講師 (00365446)
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| Co-Investigator(Kenkyū-buntansha) |
IMOTO Masaya 慶應義塾大学, 理工学部, 教授 (60213253)
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| Project Period (FY) |
2008 – 2010
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| Project Status |
Completed (Fiscal Year 2010)
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| Budget Amount *help |
¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2010: ¥520,000 (Direct Cost: ¥400,000、Indirect Cost: ¥120,000)
Fiscal Year 2009: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000)
Fiscal Year 2008: ¥2,860,000 (Direct Cost: ¥2,200,000、Indirect Cost: ¥660,000)
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| Keywords | 小胞体ストレス / XBP1 / 固形がん悪性化 / 固形がん悪性 / タンパク質合成阻害剤 |
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| Research Abstract |
Poorly vascularized solid-tumor cells encounter a range of cytotoxic conditions such as hypoxia and nutrient deprivation, which cause ER stress. These cytotoxic conditions in solid tumors are considered to adapt to ER stress by activating X-box binding protein 1 (XBP1). Therefore, we have been screening for an inhibitor of XBP1 activation, and we succeeded to identify three small molecule inhibitors. As we investigated the molecular mechanism by which these small molecule inhibitors inhibited XBP1, we found that toyocamycin strongly inhibited XBP1 and induced apoptosis in cancer cells only under ER stressed condition. Therefore, toyocamycin would be an inhibitor as a new molecular target therapy of cancer.
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Report
(4 results)
Research Products
(62 results)
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[Journal Article] Isolation and structure elucidation of a novel androgen antagonist, arabilin, produced by Streptomyces sp.MK756-CF12010
Author(s)
T.Kawamura, T.Fujimaki, N.Hamanaka, K.Torii, H.Kobayashi, Y.Takahashi, M.Igarashi, N.Kinoshita, Y.Nishimura, E.Tashiro, M.Imoto
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Journal Title
J.Antibiot(Tokyo) 63
Pages: 601-605
Related Report
Peer Reviewed
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[Journal Article] Isolation and structure elucidation of a novel androgen antagonist, arabilin, produced by Streptomyces sp.MK756-CF12010
Author(s)
T.Kawamura, T.Fujimaki, N.Hamanaka, K.Torii, H.Kobayashi, Y.Takahashi, M.Igarashi, N.Kinoshita, Y.Nishimura, E.Tashiro, M.Imoto
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Journal Title
J.Antibiot(Tokyo)
Volume: 63
Pages: 601-605
Related Report
Peer Reviewed
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[Journal Article] SAR study of a Novel Triene-ansamycin Group Compound, Quinotrierixin, and Related Compounds, as Inhibitors of ER Stress-induced XBP1 Activation. I.Taxonomy, Fermentation, Isolation, and Biological activities and SAR study2008
Author(s)
T.Kawamura, E.Tashiro, K.Yamamoto, K Shindo, M.Imoto
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Journal Title
J.Antibiot(Tokyo) 61
Pages: 303-311
Related Report
Peer Reviewed
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[Journal Article] Discovery of Incednine as a Potent Modulator of the Anti-apoptotic Function of Bcl-xL from Microbial Origin2008
Author(s)
Y.Futamura, R.Sawa, Y.Umezawa, M.Igarashi, H.Nakamura, K.Hasegawa, M.Yamasaki, E.Tashiro, Y.Takahashi, Y.Akamatsu, M.Imoto
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Journal Title
The Journal of American Chemical Society 130
Pages: 1822-1823
Related Report
Peer Reviewed
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