2013 Fiscal Year Final Research Report
Study on senescence-associated tumor promotion
| Project/Area Number |
23300352
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| Research Category |
Grant-in-Aid for Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Tumor biology
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| Research Institution | Japanese Foundation for Cancer Research |
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Principal Investigator |
HARA Eiji 公益財団法人がん研究会, がん研究所がん生物部, 部長 (80263268)
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| Project Period (FY) |
2011-04-01 – 2014-03-31
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| Keywords | 細胞老化 / 発癌 / 細胞周期 / ROS |
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| Research Abstract |
Cellular senescence was known to be associated with increased levels of reactive oxygen species (ROS), carcinogen known to cause DNA damage. However, molecular mechanisms underlying the increased ROS production has remained unclear. Here, we show that the cross-talk between the p16-RB-pathway and AKT-pathway determines ROS level by controlling the overlapping functions of FoxM1 and FoxO3a, transcription factors known to regulate ROS scavenger expression. We also demonstrate here that this pathway operates not only in cultured fibroblasts but also in mouse liver, indicating that this machinery may contribute broadly to tumorigenesis in vivo.
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[Journal Article] Crosstalk between the Rb pathway and AKT signaling forms a quiescence-senescence switch2014
Author(s)
Imai, Y., Takahashi, A., Hanyu, A., Sato, S., Naka, K., Hirao, A., Ohtani, N., Hara, E
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Journal Title
Cell Reports
Volume: 7
Pages: 194-1207
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[Journal Article] Obesity-induced gut microbial metabolite promotes liver cancer through senescence secretome2013
Author(s)
Yoshimoto, S., Loo, T. M., Atarashi, K., Kanda, H., Sato, S., Oyadomari, S., Iwakura, Y., Oshima, K., Morita, H., Hattori, M., Ishikawa, Y., Hara, E., Ohtani, N
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Journal Title
Nature
Volume: 499
Pages: 97-101
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[Journal Article] Development of mice without Cip/Kip CDK inhibitors2012
Author(s)
Tateishi, Y., Matsumoto. A., Kanie, T., Hara, E., Nakayama, K., Nakayama, K.I
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Journal Title
Biochem. Biophys. Res. Commun
Volume: 427
Pages: 285-292
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[Journal Article] DNA damage signaling triggers degradation of histone methyltransferases through APC/C^<Cdh1> in senescent cells2012
Author(s)
Takahashi, A., Imai, Y., Yamakoshi, K., Kuninaka, S., Ohtani, N., Yoshimoto, S., Hori, S., Tachibana, M., Anderton, E., Takeuchi, T., Shinkai, Y., Peters, G., Saya, H. and Hara E
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Journal Title
Mol. Cell
Volume: 45
Pages: 123-131
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[Journal Article] Protein kinase A determines timing of early differentiation through epigenetic regulation with G9a2012
Author(s)
Yamamizu, K., Fujihara, M., Tachibana, M., Katayama, S., Takahashi, A., Hara, E., Imai, H., Shinkai, Y., and Yamashita, J. K
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Journal Title
Cell Stem Cell
Volume: 10
Pages: 759-770
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[Journal Article] E2FBP1 antagonizes the p16(INK4A)-Rb tumor suppressor machinery for growth suppression and cellular senescence by regulating promyelocytic leukemia protein stability2011
Author(s)
Fukuyo, Y., Takahashi, A., Hara, E., Horikoshi, N., Pandita, T. K., Nakajima, T
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Journal Title
Int J Oral Sci
Volume: 3
Pages: 200-208
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