Exploring novel genes that regulate glycolysis using a genome-wide siRNA library

• Project/Area Number: 22790846
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Metabolomics
• Research Institution: The University of Tokyo
• Principal Investigator: SAKAMOTO Takeharu 東京大学, 医科学研究所, 助教 (70511418)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: 解糖系 / siRNAライブラリー / 癌細胞 / マクロファージ

Research Abstract

Glycolysis is a system of energy production which plays an important role in many diseases such as cancer and inflammatory diseases. However, how glycolysis is regulated remains unclear. To address this, we explored novel genes that regulate glycolysis using a genome-wide siRNA library, and identified novel 19 genes. Some of these genes regulate cancer cell growth or macrophage function. Therefore, these genes we identified in this study might be therapeutic targets for cancer or inflammatory diseases.

Research Products

• [Journal Article] Genetic Screening of New Genes Responsible for Cellular Adaptation to Hypoxia Using a Genome-Wide shRNA Library (2012)
  • Author(s): Yoshino S, Hara T, Weng JS, Takahashi Y, Seiki M, Sakamoto T
  • Journal Title: PloS one Volume: 7
  • URL: http://dx.plos.org/10.1371/journal.pone.0035590
  • Peer Reviewed
• [Journal Article] Genetic screening of new genes responsible for cellular adaptation to hypoxia using a genome-wide shRNA library (2012)
  • Author(s): Yoshino S, Hara T, Weng JS, Takahashi Y, Seiki M, Sakamoto T
  • Journal Title: PLoS ONE Volume: (印刷中)
  • Peer Reviewed
• [Journal Article] Genetic dissection of proteolytic and non-proteolytic contributions of MT1-MMP to macrophage invasion (2011)
  • Author(s): Hara T, Mimura K, Seiki M, Sakamoto T
  • Journal Title: Biochemical and biophysical research communications Volume: 413 Pages: 277-281
  • Peer Reviewed
• [Journal Article] Deletion of the Mint3/Apba3 gene in mice abrogates macrophage functions and increases resistance to lipopolysaccharide-induced septic shock (2011)
  • Author(s): Hara T, Mimura K, Abe T, Shioi G, Seiki M, Sakamoto T
  • Journal Title: The Journal of biological chemistry Volume: 286 Pages: 32542-32551
  • Peer Reviewed
• [Journal Article] Targeting the Warburg effect that arises in tumor cells expressing membrane type-1 matrix metalloproteinase (2011)
  • Author(s): Sakamoto T, Niiya D, Seiki M
  • Journal Title: The Journal of biological chemistry Volume: 286 Pages: 14691-14704
  • Peer Reviewed
• [Journal Article] ZF21 is a new regulator of focal adhesion disassembly and a potential member of the spreading initiation center (2011)
  • Author(s): Nagano M, Hoshino D, Sakamoto T, Akizawa T, Koshikawa N, Seiki M
  • Journal Title: Cell adhesion & migration Volume: 5 Pages: 23-28
  • Peer Reviewed
• [Journal Article] Genetic dissection of proteolytic and non-proteolytic contributions of MT1-MMP to macrophage invasion. (2011)
  • Author(s): Hara T, Mimura K, Seiki M, Sakamoto T.
  • Journal Title: Biochem Biophys Res Commun. Volume: 23;413(2) Issue: 2 Pages: 277-81
  • DOI: 10.1016/j.bbrc.2011.08.085
  • Peer Reviewed
• [Journal Article] Deletion of the Mint3/Apba3 gene in mice abrogates macrophage functions and increases resistance to lipopolysaccharide-induced septic shock (2011)
  • Author(s): Hara T, Mimura K, Abe T, Shioi G, Seiki M, Sakamoto T.
  • Journal Title: J Biol Chem. Volume: 16;286(37) Issue: 37 Pages: 32542-51
  • DOI: 10.1074/jbc.m111.271726
  • Peer Reviewed
• [Journal Article] Targeting the Warburg effect that arises in tumor cells expressing membrane type-1 matrix (2011)
  • Author(s): Sakamoto T, Niiya D, Seiki M
  • Journal Title: metalloproteinase. Volume: J Biol Chem 22;286(16) Issue: 16 Pages: 14691-704
  • DOI: 10.1074/jbc.m110.188714
  • Peer Reviewed
• [Journal Article] ZF21 is a new regulator of focal adhesion disassembly and a potential member of the spreading initiation center. (2011)
  • Author(s): Nagano M, Hoshino D, Sakamoto T, Akizawa T, Koshikawa N, Seiki M.
  • Journal Title: Cell Adh Migr. Volume: 5(1) Pages: 23-28
  • Peer Reviewed
• [Journal Article] ZF21 protein regulates cell adhesion and motility (2010)
  • Author(s): Nagano M, Hoshino D, Sakamoto T, Kawasaki N, Koshikawa N, Seiki M
  • Journal Title: The Journal of biological chemistry Volume: 285 Pages: 21013-21022
  • Peer Reviewed
• [Journal Article] A membrane protease regulates energy production in macrophages by activating hypoxia-inducible factor-1 via a non-proteolytic mechanism (2010)
  • Author(s): Sakamoto T, Seiki M
  • Journal Title: The Journal of biological chemistry Volume: 285 Pages: 29951-29964
  • Peer Reviewed
• [Journal Article] A membrane protease regulates energy production in macrophages by activating hypoxia-inducible factor-1 via a non-proteolytic mechanism. (2010)
  • Author(s): Sakamoto T, Seiki M.
  • Journal Title: J Biol Chem. Volume: 285(39) Pages: 29951-64
  • Peer Reviewed
• [Journal Article] ZF21 protein regulates cell adhesion and motility. (2010)
  • Author(s): Nagano M, Hoshino D, Sakamoto T, Kawasaki N, Koshikawa N, Seiki M.
  • Journal Title: J Biol Chem. Volume: 285(27) Pages: 21013-22
  • Peer Reviewed
• [Presentation] Mint3 is a new molecular target for metastasis suppression (2012)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: The 16th JFCR-ISCC
  • Place of Presentation: 東京
  • Year and Date: 2012-01-25
• [Presentation] Targeting the Warburg effect that arises in tumor cells expressing membrane type-1 matrix metalloprotease (2011)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 横浜
  • Year and Date: 2011-12-15
• [Presentation] Ubiquitin ligase RNF126 serves as a gate keeper from glycolysis to oxidative phosphorylation and regulates tumor growth (2011)
  • Author(s): Seiko Yoshino, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川
  • Year and Date: 2011-12-15
• [Presentation] Targeting the Warburg effect that arises in tumor cells expressing membrane type-1 matrix metalloprotease (2011)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川
  • Year and Date: 2011-12-15
• [Presentation] Mint3 in tumor stromal cells promotes tumor metastasis (2011)
  • Author(s): Kouhei Mimura, Toshiro Hara, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川
  • Year and Date: 2011-12-14
• [Presentation] Analysis of the regulatory mechanism of HIF-1 activation by Mint3 during normoxia (2011)
  • Author(s): Jane S.Weng, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川
  • Year and Date: 2011-12-14
• [Presentation] Deletion of the Mint3/Apba3 Gene in Mice Abrogates Macrophage Functions and Increases Resistance to Lipopolysaccharide-induced Septic Shock (2011)
  • Author(s): Toshiro Hara, Kouhei Mimura, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第34回日本分子生物学会年会
  • Place of Presentation: 神奈川
  • Year and Date: 2011-12-14
• [Presentation] Mint3/APBA3 regulating HIF-1 activation in macrophages play a critical role in LPS-induced septic shock in a mouse model (2011)
  • Author(s): Toshiro Hara, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-05
• [Presentation] ZF21, a novel focal adhesion-related protein, promotes cancer cell invasion (2011)
  • Author(s): Makoto Nagano, Daisuke Hoshino, Takeharu Sakamoto, Rika Okihara, Motomi Konishi, Naohiko Koshikawa, Toshifumi Akizawa, Motoharu Seiki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-05
• [Presentation] Targeting the Warburg effect that arises in tumor cells expressing membrane type-1 matrix metalloprotease (2011)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2011-10-04
• [Presentation] Ubiquitin ligase RNF126 serves as a gate keeper from glycolysis to oxidative phosphorylation and regulates tumor growth (2011)
  • Author(s): Seiko Yoshino, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-04
• [Presentation] Targeting the Warburg effect that arises in tumor cells expressing membrane type-1 matrix metalloprotease (2011)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-04
• [Presentation] Analysis of the regulatory mechanism of HIF-1 activation by Mint3 during normoxia (2011)
  • Author(s): Jane S.Weng, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-04
• [Presentation] Mint3 in tumor stromal cells promotes tumor metastasis (2011)
  • Author(s): Kouhei Mimura, Toshiro Hara, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 愛知
  • Year and Date: 2011-10-03
• [Presentation] Deletion of the Mint3 gene in mice abrogates macrophage functions and increases resistance to cancer metastasis (2011)
  • Author(s): 原敏朗、三村耕平、坂本毅治、清木元治
  • Organizer: 平成23年度がん若手研究者ワークショップ
  • Place of Presentation: 長野
  • Year and Date: 2011-09-02
• [Presentation] Ring finger protein 126, RNF126, is a new E3 ubiquitin ligase that serves as a gate keeper from glycolysis to oxidative phosphorylation and regulates tumor growth (2011)
  • Author(s): 芳野聖子、坂本毅治、清木元治
  • Organizer: 平成23年度がん若手研究者ワークショップ
  • Place of Presentation: 長野
  • Year and Date: 2011-09-01
• [Presentation] MT1-MMP/Mint3は通常酸素下でHIF-1を活性化しマクロファージおよび癌細胞の解糖系を亢進させる (2011)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 日本がん分子標的治療学会第15回学術集会
  • Place of Presentation: 東京
  • Year and Date: 2011-06-25
• [Presentation] Mint3 regulates macrophage functions in vitro and in vivo by suppressing FIH-1 (2010)
  • Author(s): Toshiro Hara, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] Idenitification of novel genes that mediate hypoxic adaptation using a genome-wide siRNA screening in cancer cells (2010)
  • Author(s): Seiko Yoshino, Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-08
• [Presentation] A membrane protease regulates energy production in macrophages by activating Hypoxia-Inducible Factor-1 via a non-proteolytic mechanism (2010)
  • Author(s): Takeharu Sakamoto and Motoharu Seiki
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸
  • Year and Date: 2010-12-07
• [Presentation] A membrane protease regulates energy production in macrophages by activating Hypoxia-Inducible Factor-1 via a non-proteolytic mechanism (2010)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートアイランド
  • Year and Date: 2010-12-07
• [Presentation] ゲノムワイドsiRNAライブラリーを用いた新規低酸素適応因子の同定 (2010)
  • Author(s): 芳野聖子、坂本毅治、清木元治
  • Organizer: 第69回日本癌学会学術会議
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-24
• [Presentation] A membrane protease regulates energy production in macrophages by activating Hypoxia-Inducible Factor-1 via a non-proteolytic mechanism (2010)
  • Author(s): Takeharu Sakamoto and Motoharu Seiki
  • Organizer: 第69回日本癌学会学術会議
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-22
• [Presentation] A membrane protease regulates energy production in macrophages by activating Hypoxia-Inducible Factor-1 via a non-proteolytic mechanism (2010)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第69回日本癌学会学術会議
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2010-09-22
• [Presentation] MT1-MMP/Mint3 axis augments glycolysis in macrophages and cancer cells (2010)
  • Author(s): Takeharu Sakamoto and Motoharu Seiki
  • Organizer: 「がん研究分野の特性等を踏まえた支援活動」がん若手ワークショップ
  • Place of Presentation: 蓼科
  • Year and Date: 2010-09-03
• [Presentation] MT1-MMP/Mint3 axis augments glycolysis in macrophages and cancer cells (2010)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 「がん研究分野の特性等を踏まえた支援活動」がん若手ワークショップ
  • Place of Presentation: アートランドホテル蓼科
  • Year and Date: 2010-09-03
• [Presentation] Mint3 enhances the activity of HIF-1 in macrophages by suppressing the activity of FIH-1 (2010)
  • Author(s): Takeharu Sakamoto and Motoharu Seiki
  • Organizer: 第19回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢
  • Year and Date: 2010-06-16
• [Presentation] Mint3 enhances the activity of HIF-1 in macrophages by suppressing the activity of FIH-1 (2010)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 第19回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2010-06-16
• [Presentation] ゲノムワイドsiRNAライブラリーを用いた新規低酸素適応因子の同定 (2010)
  • Author(s): 芳野聖子、坂本毅治、清木元治
  • Organizer: 第19回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2010-06-16
• [Presentation] A novel FIH-1 suppresser, Mint3 regulates macrophage functions in vitro and in vivo (2010)
  • Author(s): 原敏朗、坂本毅治、清木元治
  • Organizer: 第19回日本がん転移学会学術集会・総会
  • Place of Presentation: 金沢市文化ホール
  • Year and Date: 2010-06-16
• [Presentation] Mint3 enhances the activity of HIF-1 in macrophages by suppressing the activity of FIH-1 (2010)
  • Author(s): Takeharu Sakamoto and Motoharu Seiki
  • Organizer: 18th International Symposium on Molecular Cell Biology of Macrophages
  • Place of Presentation: 熊本
  • Year and Date: 2010-05-20
• [Presentation] Mint3 enhances the activity of HIF-1 in macrophages by suppressing the activity of FIH-1 (2010)
  • Author(s): Takeharu Sakamoto, Motoharu Seiki
  • Organizer: 18th International Symposium on Molecular Cell Biology of Macrophages 2010
  • Place of Presentation: Kumamoto Parea Hall, Kumamoto, Japan
  • Year and Date: 2010-05-20
• [Book] がんの浸潤・転移第20章 (2011)
  • Author(s): 坂本毅治・清木元治、南山堂
  • Publisher: 細胞外マトリックス(ECM)
• [Book] がんの浸潤・転移第20章細胞外マトリックス(ECM) (2011)
  • Author(s): 坂本毅治・清木元治
  • Publisher: 南山堂
• [Remarks]
  • URL: http://www.motoharu-seiki.com/
• [Remarks]
  • URL: http://www.motoharu-seiki.com/