Elucidation of a novel regulatory axis of glycolysis in cancer stem cells based on cancer genomics database analysis
| Project/Area Number |
20K07207
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Review Section |
Basic Section 47060:Clinical pharmacy-related
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| Research Institution | Tokyo University of Science |
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Principal Investigator |
Akimoto Kazunori 東京理科大学, 薬学部生命創薬科学科, 教授 (70285104)
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| Project Period (FY) |
2020-04-01 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000)
Fiscal Year 2022: ¥910,000 (Direct Cost: ¥700,000、Indirect Cost: ¥210,000)
Fiscal Year 2021: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000)
Fiscal Year 2020: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
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| Keywords | 癌の層別化 / 公共の癌ゲノムデータ / 癌幹細胞 / 解糖系 / データサイエンス手法 / 層別化 / 公共の癌ゲノミクスデータ / ALDH1陽性乳癌幹細胞 / 癌ゲノム医療 / 患者層別化 |
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| Outline of Research at the Start |
癌ゲノム医療の限界は、限られた種類の遺伝子変異パネルに依拠していることである。癌ゲノム医療を進展させるためには、更なる有用な遺伝子変異情報に加え、遺伝子発現パターン等の情報も加え、詳細に癌患者を層別化する必要がある。これを裏付けるのは、癌ゲノムデータ解析によって抽出した事象と癌との因果関係を証明することである。申請者は、癌ゲノムデータ解析を起点とし、PKCλ依存的な癌幹細胞における新規解糖系制御機構の存在を突き止めた。そこで、本申請研究において、未解決課題の解明に取り組み、複雑な癌幹細胞代謝機構の新たな側面を明らかにし、患者層別化に寄与することで、より精密な癌ゲノム医療の発展に貢献する。
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| Outline of Final Research Achievements |
It is revealed the details of a new glycolytic regulatory mechanism. Specifically, direct phosphorylation of transcription factor X by PKCλ is involved in the intracellular stabilization of protein X by avoiding proteasomal degradation, and that this mechanism is related to the glycolytic and pentose phosphate pathways and was one of the major regulatory mechanisms of their pathways in ALDH1-positive breast cancer stem cells. In addition, it was also revealed that the novel mechanism is involved in the asymmetric cell division of ALDH1-positive cancer stem cells, and a new stratification of breast cancer has also progressed. The series of the results will contribute to the detailed understanding on the glycolytic and drug metabolisms of cancer stem cells, as well as the development of new biomarkers and molecular targeted drugs for cancer.
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| Academic Significance and Societal Importance of the Research Achievements |
公共の癌ゲノムデータベース解析を起点にしてデータサイエンス手法（主に統計学的手法とバイオインフォマティクス）と癌生物学的手法を融合するかたちで研究を進めた。一連の研究成果は、乳癌の新たな層別化とともに、癌幹細胞の糖代謝機構や薬物代謝機構の研究の進展に寄与する。本研究で用いたアプローチはグローバルで蓄積しつつある公共のビッグデータや医療データの解析研究に新たな切り口を提供するとともに、癌の新たなバイオマーカーや分子標的の同定に役立ち、癌治療における新たな診断法や治療薬の開発に貢献する。
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Report
(3 results)
Research Products
(30 results)
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[Journal Article] Transcriptomic and Functional Evidence Show Similarities between Human Amniotic Epithelial Stem Cells and Keratinocytes2022
Author(s)
Li-Ping Liu, Dong-Xu Zheng, Zheng-Fang Xu, Hu-Cheng Zhou, Yun-Cong Wang, Hang Zhou, Jian-Yun Ge, Daisuke Sako, Mi Li, Kazunori Akimoto, Yu-Mei Li, and Yun-Wen Zheng
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Journal Title
Cells
Volume: 11
Issue: 1
Pages: 70-70
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Glyoxalase 1 and protein kinase Cλ as potential therapeutic targets for late-stage breast cancer.2021
Author(s)
Motomura H, Ozaki A, Tamori S, Onaga C, Nozaki Y, Waki Y, Takasawa R, Yoshizawa K, Mano Y, Sato T, Sasaki K, Ishiguro H, Miyagi Y, Nagashima Y, Yamamoto K, Sato K, Hanawa T, Tanuma SI, Ohno S, Akimoto K
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Journal Title
Oncol Lett.
Volume: 22
Issue: 1
Pages: 547-547
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] GLO 1 and PKCλ Regulate ALDH1-positive Breast Cancer Stem Cell Survival.2021
Author(s)
Motomura H, Tamori S, Yatani MA, Namiki A, Onaga C, Ozaki A, Takasawa R, Mano Y, Sato T, Hara Y, Sato K, Xiong Y, Harada Y, Hanawa T, Tanuma SI, Sasaki K, Ohno S, Akimoto K.
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Journal Title
Anticancer Res.
Volume: 41
Issue: 12
Pages: 5959-5971
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] High SLC20A1 expression is associated with poor prognosis in claudin-low and basal-like breast cancers2021
Author(s)
Onaga C., Tamori S., Motomura H., Ozaki A., Matsuda C., Matsuoka I., Fujita T., Nozaki Y., Hara Y., Kawano Y., Harada Y., Sato T., Mano Y., Sato K., Akimoto K.
Organizer
International Research Network Initiative (IRNI) & International Postgraduate Conference on Pharmaceutical Sciences (IPoPS) 2021
Related Report
Int'l Joint Research
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