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Analysis of a mechanism of Girdin-mediated regulation of cancer cell metabolism

研究課題

研究課題/領域番号 17K17791
研究種目

若手研究(B)

配分区分基金
研究分野 実験病理学
病態医化学
研究機関名古屋大学

研究代表者

翁 良  名古屋大学, 医学系研究科, 特任助教 (20729280)

研究期間 (年度) 2017-04-01 – 2018-03-31
研究課題ステータス 中途終了 (2017年度)
配分額 *注記
4,290千円 (直接経費: 3,300千円、間接経費: 990千円)
2018年度: 1,560千円 (直接経費: 1,200千円、間接経費: 360千円)
2017年度: 2,730千円 (直接経費: 2,100千円、間接経費: 630千円)
キーワードcancer metabolism / Girdin / actin cytoskeleton / PKM2 / glycolysis
研究実績の概要

The previous work from our laboratory characterized the actin-binding protein Girdin as a critical regulator of migration of endothelial cells, cancer cells, and neuroblasts, which depends on extracellular cues including growth factor stimulation. We also previously found that Girdin also interacts with amino acids transporters to regulate amino acids-induced mTORC1 activation. To further investigate the role of Girdin in cancer metabolism, we employed affinity column chromatography to isolate Girdin-interacting proteins, and identified Pyruvate Kinase M2 (PKM2), a key enzyme that regulates the Warburg effect that is necessary for tumor growth, as a candidate. The interaction of PKM2 with Girdin was confirmed by co-immunoprecipitation (co-IP), western blot analysis and immunofluorescence. Next, to check on the role of Girdin in cancer metabolism, we evaluated the effect of Girdin depletion on ATP and lactate production, and glucose consumption by commercially available biochemical kits. We also investigated the role of Girdin in PKM2 Y105 phosphorylation, which is highly related to PKM2 enzyme activity. We also analyzed the role of Girdin in lung cancer progression through IHC, where we found that the expression of Girdin is correlated with the expression of PKM2 in lung cancer tissue. In summary, the data we got from the study revealed the role of Girdin in cancer metabolism and cancer progression, and showed the possibility that Girdin is involved in the modulation of chemotherapy effect through affecting aerobic glycolysis.

報告書

(1件)
  • 2017 実績報告書
  • 研究成果

    (3件)

すべて 2018 2017

すべて 雑誌論文 (2件) (うち国際共著 1件、 査読あり 2件、 オープンアクセス 2件) 学会発表 (1件)

  • [雑誌論文] Negative regulation of amino acid signaling by MAPK-regulated 4F2hc/Girdin complex2018

    • 著者名/発表者名
      Liang Weng , Yi-Peng Han, Atsushi Enomoto, Yasuyuki Kitaura, Shushi Nagamori, Yoshikatsu Kanai, Naoya Asai, Jian An, Maki Takagishi, Masato Asai, Shinji Mii, Takashi Masuko, Yoshiharu Shimomura, Masahide Takahashi.
    • 雑誌名

      PLoS Biology

      巻: 16 号: 3 ページ: e2005090-e2005090

    • DOI

      10.1371/journal.pbio.2005090

    • 関連する報告書
      2017 実績報告書
    • 査読あり / オープンアクセス / 国際共著
  • [雑誌論文] Daple Coordinates Planar Polarized Microtubule Dynamics in Ependymal Cells and Contributes to Hydrocephalus2017

    • 著者名/発表者名
      Maki Takagishi, Masato Sawada, Shinya Ohata, Naoya Asai, Atsushi Enomoto, Kunihiko Takahashi, Liang Weng, Kaori Ushida, Hosne Ara, Shigeyuki Matsui, Kozo Kaibuchi,3Kazunobu Sawamoto, and Masahide Takahashi.
    • 雑誌名

      Cell Reports

      巻: 20 号: 4 ページ: 960-972

    • DOI

      10.1016/j.celrep.2017.06.089

    • 関連する報告書
      2017 実績報告書
    • 査読あり / オープンアクセス
  • [学会発表] Girdin regulates the collective migration of cancer cells by interacting with beta-catenin/alpha-catenin2017

    • 著者名/発表者名
      Xiaoze Wang、Atsushi Enomoto、Liang Weng、Naoya Asai、Masahide Takahashi
    • 学会等名
      第76回日本癌学会学術総会、パシフィコ横浜(神奈川県横浜市)
    • 関連する報告書
      2017 実績報告書

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公開日: 2017-04-28   更新日: 2018-12-17  

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