Elucidation of molecular mechanisms underlying colorectal tumorigenesis driven by Wnt/c-Myc signaling
| Project/Area Number |
16H04692
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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 | The University of Tokyo |
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Principal Investigator |
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| Project Period (FY) |
2016-04-01 – 2019-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥16,900,000 (Direct Cost: ¥13,000,000、Indirect Cost: ¥3,900,000)
Fiscal Year 2018: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000)
Fiscal Year 2017: ¥5,720,000 (Direct Cost: ¥4,400,000、Indirect Cost: ¥1,320,000)
Fiscal Year 2016: ¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
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| Keywords | Wnt / c-Myc / lncRNA |
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| Outline of Final Research Achievements |
We identified a direct target of c-Myc, termed MYU, and showed that MYU was upregulated in most colon cancers and required for the tumorigenicity of colon cancer cells. Furthermore, we demonstrated that MYU associated with the RNA binding protein hnRNP-K to stabilize CDK6 expression and thereby promoted the G1-S transition of the cell cycle. These results suggest that the MYU/hnRNP-K/CDK6 pathway functions downstream of Wnt/c-Myc signaling and plays a critical role in the proliferation and tumorigenicity of colon cancer cells.
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| Academic Significance and Societal Importance of the Research Achievements |
転写因子であるc-Mycは様々なシグナル経路のハブ因子として機能することが知られています。そのため、c-Mycを直接阻害する薬剤は大きな副作用があると予想されます。したがって、c-Mycが誘発するがんに対してはMYU、hnRNP-K、CDK6による情報伝達の仕組みががんの分子標的薬を創製する上で重要な標的に成り得ると期待できました。
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Report
(4 results)
Research Products
(16 results)
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[Journal Article] Long noncoding RNA UPAT promotes colon tumorigenesis by inhibiting degradation of UHRF12016
Author(s)
Taniue K, Kurimoto A, Sugimasa H, Nasu E, Takeda Y, Iwasaki K, Nagashima T, Okada-Hatakeyama M, Oyama M, Kozuka-Hata H, Hiyoshi M, Kitayama J, Negishi L, Kawasaki Y, Akiyama T.
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Journal Title
Proc. Natl. Acad. Sci. U S A.
Volume: 113
Pages: 1273-1278
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Temporal Profiling of Astrocyte Precursors Reveals Parallel Roles for Asef during Development and after Injury2016
Author(s)
Chaboub LS, Manalo JM, Lee HK, Glasgow SM, Chen F, Kawasaki Y, Akiyama T, Kuo CT, Creighton CJ, Mohila CA, Deneen B
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Journal Title
J. Neurosci.
Volume: 36
Pages: 11904-11917
Related Report
Peer Reviewed / Int'l Joint Research
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[Journal Article] MYU, a target lncRNA for Wnt/c-Myc signaling, mediates induction of CDK6 to promote cell cycle progression2016
Author(s)
Kawasaki Y, Komiya M, Matsumura K, Negishi L, Suda S, Okuno M, Yokota N, Osada T, Nagashima T, Hiyoshi M, Okada-Hatakeyama M, Kitayama J, Shirahige K, Akiyama T.
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Journal Title
Cell Rep
Volume: 16(10)
Pages: 2554-2564
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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