Analysis of molecular mechanisms of cell proliferation in BAP1-mutated cancer using synthetic lethal phenotypes
| Project/Area Number |
18K06979
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 49010:Pathological biochemistry-related
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| Research Institution | Tokyo University of Technology (2019-2020)
Juntendo University (2018) |
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Principal Investigator |
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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 |
¥4,420,000 (Direct Cost: ¥3,400,000、Indirect Cost: ¥1,020,000)
Fiscal Year 2020: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
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| Keywords | 合成致死 / 悪性中皮腫 / DNA損傷修復 / BAP1 |
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| Outline of Final Research Achievements |
We analyzed USP1 and CHK2 among the genes that showed synthetic lethal phenotype for BAP1 mutation in cultured cells.The following results were obtained. (1) FANCD2, which has been reported as a target protein of the deubiquitinating enzyme USP1, is also deubiquitinated in BAP1 in vitro, (2) knockdown of BAP1 in malignant mesothelioma cell lines delays the S phase, and (3) inhibiting USP1/CHK2 blocks cancer growth in tumor-bearing mice using BAP1 mutant cells.
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| Academic Significance and Societal Importance of the Research Achievements |
BAP1遺伝子はがん抑制遺伝子であるため、その変異によって起こるがんに対する抗がん剤開発では直接標的にしにくいという問題がある。そこで合成致死表現型を用い、将来的に標的になる可能性がある分子標的の探索をするとともに、候補遺伝子の新しい機能を解析した。
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Report
(4 results)
Research Products
(26 results)
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[Presentation] CAGE transcriptome analysis reveals BCL2A1 upregulation in FLT3-ITD/D835 dual mutated AML cells harboring complex co-mutations2019
Author(s)
Kotoko Yamatani, Tomohiko Ai, Kaori Saitoh, Haeun Yang, Koya Suzuki,Atsushi Hori, Yuko Murakami-Tonami, Weiguo Zhang, Bing Carter, Sonoko Kinjo, Kazuho Ikeo, Kazuhiro Katayama, Yoshikazu Sugimoto, Hironori Harada, Takashi Miida, Neil P. Shah, Marina Konopleva, Yoshihide Hayashizaki, Michael Andreeff, Yoko Tabe
Organizer
61st ASH (American Society of Hematology) Meeting
Related Report
Int'l Joint Research
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[Presentation] OxPhos inhibition induces formation of tunneling nanotubes in AML cells and facilitates mitochondrial transfer from BM stroma to AML that contributes to microenvironment-mediated drug-resistance of AML2019
Author(s)
Haeun Yang, Yoko Tabe, Kaori Saitoh, Kotoko Yamatani, Rodrigo Jacamo, Helen Ma, Vivian Ruvolo, Qi Zhang, Vinitha Kuruvilla, Natalia Baran, Junichi Imoto, Kazuho Ikeo, Kaori Moriya, Yuko Murakami-Tonami, Koya Suzuki, Takashi Miida, Michael Andreeff, Christopher Vellano, Joseph R. Marszalek, Marina Konopleva
Organizer
61st ASH (American Society of Hematology) Meeting
Related Report
Int'l Joint Research
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[Presentation] Upregulation of Bcl-2 confers resistance to FLT3 inhibition in FLT3-ITD AML with secondary acquired mutations.2018
Author(s)
Kotoko Yamatani, Yoko Tabe, Kaori Saitoh, Haeun Yang, Yuko Tonami-Murakami, Koya Suzuki, Weiguo Zhang, Sonoko Kinjo, Kazuho Ikeo, Kaoru Mogushi, Masaki Hosoya, Shigeo Yamaguchi, Hironori Harada9, Takashi Miida, Neil P. Shah, Yoshihide Hayashizaki, Marina Konopleva, Michael Andreeff
Organizer
61st American Society of Hematology Annual Meeting 2018
Related Report
Int'l Joint Research
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[Presentation] Combined targeting of Bcl-2 and XPO1 overcomes acquired resistance to tyrosine kinase inhibitors in FLT3-ITD/TKD double mutant AML.2018
Author(s)
Yoko Tabe, Kotoko Yamatani, Haeun Yang, Kaori Saito, Yuko Tonami-Murakami, Koya Suzuki, Weiguo Zhang, Sonoko Kinjo, Kazuho Ikeo, Masaki Hosoya, Kaoru Mogushi, Shigeo Yamaguchi, Hironori Harada, Takashi Miida, Neil P. Shah, Yoshihide Hayashizaki, Marina Konopleva, Michael Andreeff
Organizer
61st American Society of Hematology Annual Meeting 2018
Related Report
Int'l Joint Research
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