2012 Fiscal Year Final Research Report
Identification of regulatory system for cancer stemness and pplication to cancer therapeutics.
| Project/Area Number |
23701063
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| Research Category |
Grant-in-Aid for Young Scientists (B)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Tumor biology
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| Research Institution | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2011 – 2012
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| Keywords | 幹細胞 |
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| Research Abstract |
Methylation events driven by histone methyltransferases have been implicated in gene silencing and carcinogenesis. We focused on histone methyltransferases related to cancer stemness. In this project, we show that epigenetic silencing of KLF2 occurs in cancer cells through direct transcriptional repression mediated by the histone methyltransferase, Enhancer of Zeste Homolog 2 (EZH2). The transfection of KLF2 in cells with EZH2-associated silencing showed a significant anti-tumoral effect, both in culture and in xenografted nude mice. Most importantly, the translation of the described results to human primary samples demonstrated that patients with prostate or breast tumors with low levels of KLF2 and high expression of EZH2 had a shorter overall survival. Moreover, KLF2 regulates stemness phenotype for cancer cells. Finally, we find a low molecular weight compound, which induces KLF2 gene expression using cell-based high-throughput screening system.
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[Journal Article] Silencing of theKruppel-like factor 2 by the histone methyltransferase EZH2 in human cancer2012
Author(s)
Taniguchi H, Jacinto F.V., Villanueva A, Fernandez AF, Yamamoto H, Carmona F.J, Puertas S, Marquez VE, Shinomura Y, Imai K, and Esteller M.
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Journal Title
Oncogene
Volume: 31
Pages: 1988-1994
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[Journal Article] Shinomura Y . Co-expression of laminin ss3 and γ2 chains and epigenetic inactivationof laminin α3 chain in gastric cancer2011
Author(s)
Ii M, Yamamoto H, Taniguchi H, Adachi Y, Nakazawa M, Ohashi H, Tanuma T,Sukawa Y, Suzuki H, Sasaki S, Imai K
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Journal Title
Int J Oncol
Volume: 39
Pages: 593-599
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[Journal Article] Sanchez-Cespedes M, Villanueva A, Carmona J, Sanchez-Mut JV, Berdasco M, Moreno V, Capella G, Monk D, Ballestar E, Ropero S, Martinez R, Sanchez-Carbayo M, Prosper F, Agirre X, Fraga MF, Grana O, Perez-Jurado L, Mora J, Puig S, Prat J, Badimon L, Puca AA, Meltzer SJ, Lengauer T, Bridgewater J,Bock C, Esteller M. A DNA methylation fingerprint of 1628 human samples2011
Author(s)
Fernandez AF, Assenov Y, Martin-SuberoJI, Balint B, Siebert R, Taniguchi H, Yamamoto H, Hidalgo M, Tan AC, Galm O, Ferrer I
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Journal Title
Genome Res
Volume: 22(2)
Pages: 407-19
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[Journal Article] Shinomura Y. Epigenetic inactivation of calcium-sensing receptor in colorectal carcinogenesis2011
Author(s)
Hizaki K, Yamamoto H, Taniguchi H, Adachi Y, Nakazawa M, Tanuma T, Kato N, Sukawa Y, Sanchez JV, Suzuki H, Sasaki S, Imai K
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Journal Title
Mod Pathol
Volume: 24
Pages: 876-884
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