Development of new cancer therapy strategies by promoting aberrant cell division in the presence of replication inhibitors
Project/Area Number |
15K18423
|
Research Category |
Grant-in-Aid for Young Scientists (B)
|
Allocation Type | Multi-year Fund |
Research Field |
Tumor biology
|
Research Institution | Tokyo Metropolitan Institute of Medical Science |
Principal Investigator |
KAKUSHO Naoko 公益財団法人東京都医学総合研究所, ゲノム医科学研究分野, 研究員 (30599593)
|
Project Period (FY) |
2015-04-01 – 2018-03-31
|
Project Status |
Completed (Fiscal Year 2017)
|
Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2017: ¥780,000 (Direct Cost: ¥600,000、Indirect Cost: ¥180,000)
Fiscal Year 2016: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
Fiscal Year 2015: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
|
Keywords | Cdc7キナーゼ / Wee1キナーゼ / 細胞周期 / S期 / M期 / がん細胞死 / キナーゼ阻害剤 / DNA複製 |
Outline of Final Research Achievements |
On the basis of our proposal that inhibition of S phase causes cancer cells to proceed into lethal M phase in the presence of unreplicated genomic segment, we proposed a novel cancer therapy strategy in which cancer cell death is promoted by combination of S phase inhibition and M phase promotion. We used inhibitors of Cdc7 kinase, essential for firing of replication origins in S phases, and showed that the Cdc7 inhibitor causes cell death only after cells have progressed through S phase in the presence of the inhibitor, apparently causing cancer cells to enter aberrant M phase. When combined with MK1775, the inhibitor of Wee1 kinase that inhibits M phase, Cdc7 inhibitor caused synergistic cell death effect on cancer cells including Colo205 (colon cancer) and CCRF-CEM(leukemia). HU and Aphidicolin also induced efficient cancer cell death in combination with MK1775.
|
Report
(4 results)
Research Products
(8 results)
-
-
-
[Journal Article] CDC28 phosphorylates Cac1p and regulates the association of Chromatin Assembly Factor I with chromatin.2015
Author(s)
Jeffery, D., Kakusho, N., You, Z., Gharib, M., Wyse, B., Drury, E., Weinreich, M., Thibault, P. Verreault, A., Masai, H. and *Yankulov, K.
-
Journal Title
Cell Cycle
Volume: 14
Pages: 74-85
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
[Journal Article] Rif1 binds to G-quadruplexes and suppresses replication over long distances.2015
Author(s)
Yutaka Kanoh, Seiji Matsumoto, Rino Fukatsu, Naoko Kakusho, Nobuaki Kono, Claire Renard-Guillet, Koji Masuda, Keisuke Iida, Kazuo Nagasawa, Katsuhiko Shirahige, and *Hisao Masai
-
Journal Title
Nature Struct. Mol. Biol.
Volume: 22
Pages: 889-897
DOI
Related Report
Peer Reviewed / Int'l Joint Research / Acknowledgement Compliant
-
-
-
-