| Project/Area Number |
18K19577
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Review Section |
Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
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| Research Institution | Kanazawa University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
大黒 多希子 金沢大学, 学際科学実験センター, 教授 (30767249)
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| Project Period (FY) |
2018-06-29 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,240,000 (Direct Cost: ¥4,800,000、Indirect Cost: ¥1,440,000)
Fiscal Year 2019: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2018: ¥3,250,000 (Direct Cost: ¥2,500,000、Indirect Cost: ¥750,000)
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| Keywords | 食道 / 扁平上皮がん / 発がん / 代謝酵素 / ゲノム編集 / 糖代謝酵素 |
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| Outline of Final Research Achievements |
This study attempted to generate cellular and mouse models susceptible to esophageal squamous cell (ESC) carcinogenesis by genome editing of glycogen synthase (GS) and GS kinase (GSK)3β, both regulating glycogen metabolism, based on the hypothesis that intracellular glycogen depletion is the critical selective pressure for cellular transformation and malignant evolution in ESC carcinogenesis. By genome editing technologies including CRISPR-Cas9, we could deplete GS or transduce the constitutively active mutant of GSK3β in patient-derived normal ESCs and C57BL/6 mouse esophageal squamous mucosa. Long term observations for changes in glycogen metabolism and preneoplastic phenotypes in these genome-edited human ESCs and mouse model established in the term of this research project are necessary to clarify an induction of susceptibility to ESC carcinogenesis.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究は、食道と頭頸部扁平上皮がんの連鎖に代表されるフィールドがん化現象（共通のがん誘発因子により複数の領域や組織にまたがってひろく発がんする状態）と、細胞、組織の分化や発がんにおけるグリコーゲン合成系の新たな生物学的機能の一端を拓く可能性が期待される。食道がんの90%を占める扁平上皮がんの発がん特性を外挿する自然発がんモデルの構築に新たな視点を附与することにより、健康被害を来たす本疾患の病態理解、早期診断や治療法開発に寄与することが期待される。
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