Epigallocatechin‑3‑gallate hinders metabolic coupling to suppress colorectal cancer malignancy through targeting aerobic glycolysis in cancer‑associated fibroblasts

• 資料種別: 博士論文
• タイトル: Epigallocatechin‑3‑gallate hinders metabolic coupling to suppress colorectal cancer malignancy through targeting aerobic glycolysis in cancer‑associated fibroblasts
• 著者・編者: Chen, Shuhai; Nishi, Masaaki; Morine, Yuji; Shimada, Mitsuo; Tokunaga, Takuya; Kashihara, Hideya; Takasu, Chie; Yamada, Shinichiro; Wada, Yuma
• 著者標目: Chen, Shuhai; Nishi, Masaaki; Morine, Yuji; Shimada, Mitsuo; Tokunaga, Takuya; Kashihara, Hideya; Takasu, Chie; Yamada, Shinichiro; Wada, Yuma
• 出版事項: Spandidos Publications
• 出版年月日等: 2022-01-14
• 出版年（W3CDTF）: 2022-01-14
• 並列タイトル等: EGCG HINDERS METABOLIC COUPLING BETWEEN CANCER AND CAFs; エピガロカテキン-3-ガレートはがん関連線維芽細胞における糖代謝制御することで、metabolic couplingを阻害し、大腸癌細胞の腫瘍悪性度を抑制する
• タイトル（掲載誌）: International Journal of Oncology
• 巻号年月日等（掲載誌）: 60 2
• 掲載巻: 60
• 掲載号: 2
• 掲載ページ: 19-
• ISSN（掲載誌）: ISSN : 1019-6439; ISSN : 1791-2423
• 授与機関名: 徳島大学
• 授与年月日: 2023-07-27
• 報告番号: 甲第3743号
• 学位: 博士（医学）
• 本文の言語コード: eng
• 件名標目: cancer‑associated fibroblasts; epigallocatechin‑3‑gallate; aerobic glycolysis; reverse Warburg effect; colorectal cancer
• 対象利用者: 一般
• 一般注記: In recent times, researchers working on tumor metabolism have paid increasing attention to the tumor microenvironment. Emerging evidence has confirmed that epigenetic modifications of cancer‑associated fibroblasts (CAFs) alters the characteristics of glucose metabolism to achieve a symbiotic relationship with the cancer cells. Epigallocatechin‑3‑gallate (EGCG) exerts anti‑tumor effects via a variety of mechanisms, although the underlying mechanism that accounts for the effects of EGCG on glucose metabolic alterations of CAFs have yet to be elucidated. In the present study, through co‑culture with colorectal cancer (CRC) cells, human intestinal fibroblasts were transformed into CAFs, and exhibited enhanced aerobic glycolysis. Induced CAFs were able to enhance the proliferation, migration and invasion of CRC cells in vitro. EGCG treatment led to direct inhibition of the proliferation and migration of CRC cells; furthermore, EGCG treatment of CAFs suppressed their tumor‑promoting capabilities by inhibiting their glycolytic activity. Blocking the lactic acid efflux of CAFs with a monocarboxylate transporter 4 (MCT4) inhibitor or through silencing MCT4 could also suppress their tumor‑promoting capabilities, indicating that lactate fulfills an important role in the metabolic coupling that occurs between CAFs and cancer cells. Taken together, the results of the present study showed that EGCG targeting of the metabolism of tumor stromal cells provided a safe and effective strategy of anti‑cancer therapy.
• オンライン閲覧公開範囲: インターネット公開
• 著作権情報: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License (https://creativecommons.org/licenses/by-nc-nd/4.0/).
• 関連情報（DOI）: 10.3892/ijo.2022.5309
• 連携機関・データベース: 国立情報学研究所 : 学術機関リポジトリデータベース（IRDB）（機関リポジトリ）; https://irdb.nii.ac.jp
• 提供元機関・データベース: 徳島大学 : 徳島大学機関リポジトリ

目次

http://repo.lib.tokushima-u.ac.jp/files/public/11/117318/20230824104417406707/k3743_abstract.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/117318/20230824104417626544/k3743_review.pdf fulltext

http://repo.lib.tokushima-u.ac.jp/files/public/11/117318/20230824104417775811/k3743_fulltext.pdf fulltext