Elucidation of malignant transformation based on epigenetic plasticity
| Project/Area Number |
19H01031
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| Research Category |
Grant-in-Aid for Scientific Research (A)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Review Section |
Medium-sized Section 50:Oncology and related fields
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| Research Institution | The University of Tokyo |
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Principal Investigator |
ABURATANI Hiroyuki 東京大学, 先端科学技術研究センター, 特任研究員 (10202657)
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| Project Period (FY) |
2019-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥45,110,000 (Direct Cost: ¥34,700,000、Indirect Cost: ¥10,410,000)
Fiscal Year 2022: ¥8,580,000 (Direct Cost: ¥6,600,000、Indirect Cost: ¥1,980,000)
Fiscal Year 2021: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Fiscal Year 2020: ¥11,830,000 (Direct Cost: ¥9,100,000、Indirect Cost: ¥2,730,000)
Fiscal Year 2019: ¥12,870,000 (Direct Cost: ¥9,900,000、Indirect Cost: ¥2,970,000)
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| Keywords | エピゲノム / 一細胞解析 / クロマチン / がん幹細胞 / がん |
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| Outline of Research at the Start |
腫瘍悪性化の特徴として「脱分化」あるいは「幹細胞性の獲得」等を伴う胎児形質あるいは治療抵抗性に関わるドーマンシーを示すことが挙げられる。本研究では胎児形質あるいはドーマンシーにかかわるエピゲノム可塑性の本態について、新たな制御因子としてのnon coding RNAの同定、さらには一細胞レベルでのダイナミクスを明らかにすることによって、がん悪性化メカニズム解明を目指す。
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| Outline of Final Research Achievements |
We identified a long noncoding (lnc) RNA involved in the regulation of Wnt signaling that is important for stem cell replication. This lncRNA is a direct target of β-catenin, is involved in the accessibility of the transcriptional regulatory regions of a subset of CTNNB1 targets, such as LGR5 and ASCL2, where additional transcription factor seems to bind and co-operate with CTNNB1. On the other hand, single-cell transcriptome and chromatin analyzes of reproliferating cell populations after anticancer drug treatment identified pioneer factor candidates that bind to regulatory regions that are activated prior to proliferation.
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| Academic Significance and Societal Importance of the Research Achievements |
抗がん剤治療により増殖を停止した状態でパーシスターとして残存する腫瘍細胞のコントロールはがん治療の大きな課題である。本課題において同定された幹細胞増殖に関与する新規lncRNAおよびCTNNB1と協調する転写因子、再増殖に先だって活性化されるパイオニア因子により形成される細胞増殖に関わる制御ネットワークの解明が腫瘍細胞の制御につながることが期待される。
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Report
(6 results)
Research Products
(37 results)
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[Journal Article] Multiancestry genomic and transcriptomic analysis of gastric cancer2023
Author(s)
Totoki Y, Saito-Adachi M, Shiraishi Y, Komura D, Nakamura H, Suzuki A, Tatsuno K, Rokutan H, Hama N, Yamamoto S, Ono H, Arai Y, Hosoda F, Katoh H, et al.
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Journal Title
Nature Genetics
Volume: 55
Issue: 4
Pages: 581-594
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Identification of the ultrahigh-risk subgroup in neuroblastoma cases through DNA methylation analysis and its treatment exploiting cancer metabolism2022
Author(s)
Watanabe K, Kimura S, Seki M, Isobe T, Kubota Y, Sekiguchi M, Sato-Otsubo A, Hiwatari M, Kato M, Oka A, Koh K, Sato Y, Tanaka H, Miyano S, Kawai T, Hata K, Ueno H, Nannya Y, Suzuki H, Yoshida K, Fujii Y, Nagae G, Aburatani H, Ogawa S, Takita J.
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Journal Title
Oncogene
Volume: 41
Issue: 46
Pages: 4994-5007
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Spatiotemporal dynamics of SETD5-containing NCoR-HDAC3 complex determines enhancer activation for adipogenesis2021
Author(s)
Matsumura Y, Ito R, Yajima A, Yamaguchi R, Tanaka T, Kawamura T, Magoori K, Abe Y, Uchida A, Yoneshiro T, Hirakawa H, Zhang J, Arai M, Yang C, Yang G, Takahashi H, Fujihashi H, Nakaki R, Yamamoto S, Ota S, Tsutsumi S, Inoue SI, Kimura H, Wada Y, Kodama T, Inagaki T, Osborne TF, Aburatani H, Node K, Sakai J.
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Journal Title
Nature Communications
Volume: 12
Issue: 1
Pages: 7045-7045
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Genetic and epigenetic basis of hepatoblastoma diversity.2021
Author(s)
Nagae G, Yamamoto S, Fujita M, Fujita T, Nonaka A, Umeda T, Fukuda S, Tatsuno K, Maejima K, Hayashi A, Kurihara S, Kojima M, Hishiki T, Watanabe K, Ida K, Yano M, Hiyama Y, Tanaka Y, Inoue T, Ueda H, Nakagawa H, Aburatani H, Hiyama E.
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Journal Title
Nat Commun.
Volume: 12
Issue: 1
Pages: 5423-5423
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] TET1 upregulation drives cancer cell growth through aberrant enhancer hydroxymethylation of HMGA2 in hepatocellular carcinoma.2021
Author(s)
Shirai K, Nagae G, Seki M, Kudo Y, Kamio A, Hayashi A, Okabe A, Ota S, Tsutsumi S, Fujita T, Yamamoto S, Nakaki R, Kanki Y, Osawa T, Midorikawa Y, Tateishi K, Ichinose M, Aburatani H.
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Journal Title
Cancer Sci.
Volume: 112
Issue: 7
Pages: 2855-2869
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Defined lifestyle and germline factors predispose Asian populations to gastric cancer2020
Author(s)
Suzuki A, Katoh H, Komura D, Kakiuchi M, Tagashira A, Yamamoto S, Tatsuno K, Ueda H, Nagae G, Fukuda S, Umeda T, Totoki Y, Abe H, Ushiku T, Matsuura T, Sakai E, Ohshima T, Nomura S, Seto Y, Shibata T, Rino Y, Nakajima A, Fukayama M, Ishikawa S, Aburatani H.
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Journal Title
Science Advances
Volume: 6
Issue: 19
Pages: 9778-9778
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Phosphoethanolamine Accumulation Protects Cancer Cells under Glutamine Starvation through Downregulation of PCYT22019
Author(s)
Osawa T, Shimamura T, Saito K, Hasegawa Y, Ishii N, Nishida M, Ando R, Kondo A, Anwar M, Kato K, Endo K, Yamano S, Kanki Y, Matsumura Y, Minami T, Tanaka T, Anai M, Wada Y, Wanibuchi H, Hayashi M, Hamada A, Yoshida M, Yachida S, Nakao M, Sakai J, Aburatani H, Shibuya M, Hanada K, Miyano S, Soga T, Kodama T
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Journal Title
Cell Rep.
Volume: 29(1)
Issue: 1
Pages: 89-103
DOI
Related Report
Peer Reviewed / Open Access
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