Adaptive mechanisms of cancer cells to unique growth microenvironment and therapeutic targeting

• Project/Area Number: 22300342
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Clinical oncology
• Research Institution: Japanese Foundation For Cancer Research
• Principal Investigator: TOMIDA Akihiro 公益財団法人がん研究会, がん化学療法センターゲノム研究部, 部長 (40251483)
• Project Period (FY): 2010 – 2012
• Project Status: Completed (Fiscal Year 2012)
• Budget Amount: ¥17,290,000 (Direct Cost: ¥13,300,000、Indirect Cost: ¥3,990,000); Fiscal Year 2012: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2011: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2010: ¥7,410,000 (Direct Cost: ¥5,700,000、Indirect Cost: ¥1,710,000)
• Keywords: がん細胞 / 微小環境 / グルコース飢餓 / ストレス応答 / 分子標的治療

Research Abstract

In this study, we focused on the UPR, a cellular adaptive response to glucose deprivation, that is characteristically observed in tumor microenvironment. Through the mechanistic analyses of UPR-inhibitory compounds, we elucidated that mitochondria and translation control machinery play an important role in the UPR during glucose deprivation. By evaluating the antitumor effects of the compounds, we obtained fundamental information for the therapeutic targeting of the UPR

Research Products

• [Journal Article] Compound C prevents the unfolded protein response during glucose deprivation through a mechanism independent of AMPK and BMP signaling (2012)
  • Author(s): Saito S, Furuno A, Sakurai J, Park HR, Shin-ya K, Tomida A
  • Journal Title: PLoS One Volume: 7 Issue: 9 Pages: e45845-e45845
  • DOI: 10.1371/journal.pone.0045845
  • Peer Reviewed
• [Journal Article] Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-in duced cyto toxicity during glucose deprivation (2012)
  • Author(s): Matsuo J, Tsukumo Y, Saito S, Tsukahara S, Sakurai J, Sato S, Kondo H, Ushijima M, Matsuura M, Watanabe T, Tomida A
  • Journal Title: Mol Cancer Ther Volume: 11(5) Issue: 5 Pages: 1082-1091
  • DOI: 10.1158/1535-7163.mct-11-0871
  • Peer Reviewed
• [Journal Article] Use of chemical genomics in assessment of the UPR (2011)
  • Author(s): Saito S, Tomida A
  • Journal Title: Methods Enzymol Volume: 491 Pages: 327-41
  • DOI: 10.1016/b978-0-12-385928-0.00018-3
  • ISBN: 9780123859280
• [Journal Article] Use of chemical genomics in assessment of the UPR (2011)
  • Author(s): Saito S
  • Journal Title: Methods Enzymol Volume: 491 Pages: 327-341
• [Journal Article] Identification of chrysoplenetin from Vitex negundo as a potential cytotoxic agent against PANC-1 and a panel of 39 human cancer cell lines (JFCR-39) (2011)
  • Author(s): Awale S, Linn TZ, Li F, Tezuka Y, Myint A, Tomida A, Yamori T, Esumi H, Kadota S
  • Journal Title: Phytother Res Volume: 25(12) Issue: 12 Pages: 1770-1775
  • DOI: 10.1002/ptr.3441
  • Peer Reviewed
• [Journal Article] Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity (2010)
  • Author(s): Kim JY, Hwang JH, Cha MR, Yoon MY, Son ES, Tomida A, Ko B, Song SW, Shin-ya K, Hwang YI, Park HR
  • Journal Title: J Cell Physiol Volume: 224 Issue: 1 Pages: 33-40
  • DOI: 10.1002/jcp.22085
  • Peer Reviewed
• [Journal Article] Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions (2010)
  • Author(s): Haga N, Saito S, Tsukumo Y, Sakurai J, Furuno A, Tsuruo T, Tomida A
  • Journal Title: Cancer Sci Volume: 101 Issue: 5 Pages: 1125-32
  • DOI: 10.1111/j.1349-7006.2010.01525.x
  • NAID: 10026591912
  • Peer Reviewed
• [Journal Article] Mitochondria regulate the unfolded protein response leading to cancer cell survival under glucose deprivation conditions. (2010)
  • Author(s): Haga N
  • Journal Title: Cancer Sci. Volume: 101 Pages: 1125-1132
  • Peer Reviewed
• [Journal Article] Arctigenin blocks the unfolded protein response and shows therapeutic antitumor activity. (2010)
  • Author(s): Kim JY
  • Journal Title: J Cell Physiol. Volume: 224 Pages: 33-40
  • Peer Reviewed
• [Journal Article] AP-1-Dependent miR-21 expression contributes to chemoresistance in cancer stem cell-like SP cells. (2010)
  • Author(s): Misawa A
  • Journal Title: Oncol Res. Volume: 19 Pages: 23-33
  • Peer Reviewed
• [Journal Article] Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-induced cytotoxicity during glucose deprivation
  • Author(s): Matsuo J
  • Journal Title: Mol Cancer Ther Volume: (in press)
  • Peer Reviewed
• [Presentation] Constitutive activation of hypoxic response in newly established mtDNA-deficient-cell line with highly tumorigenesis. (2013)
  • Author(s): Akihiro Tomida
  • Organizer: 9th AACR-Japanese Cancer Association Joint Conferenc
  • Place of Presentation: Maui
• [Presentation] Dorsomorphinはグルコース飢餓により誘導される小胞体ストレス応答を阻害する (2011)
  • Author(s): 冨田章弘
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-05
• [Presentation] 新規in situハイブリダイゼーション技術によるmRNA発現の判定量的解析 (2011)
  • Author(s): 冨田章弘
  • Organizer: 日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋)
  • Year and Date: 2011-10-04
• [Presentation] ビグアナイド系化合物による4E-BP1の活性化と抗腫瘍効果 (2011)
  • Author(s): 冨田章弘
  • Organizer: 日本がん分子標的治療学会学術集会
  • Place of Presentation: ホテル日航東京(東京)
  • Year and Date: 2011-06-23
• [Presentation] グルコース飢餓環境下における小胞体ストレス応答(UPR)制御薬剤の作用機序の解析 (2011)
  • Author(s): 冨田章弘
  • Organizer: 日本がん分子標的治療学会学術集会
  • Place of Presentation: ホテル日航東京(東京)
  • Year and Date: 2011-06-23
• [Presentation] Hyper activation of 4E-binding protein l by anti diabetic biguanide as its anti-tumor mechanisms of action. (2011)
  • Author(s): Tsukumo Y
  • Organizer: AACR Special Conference : Targeting of PI3K/mTOR Signaling in Cancer
  • Place of Presentation: San Francisco, CA, USA
  • Year and Date: 2011-02-26
• [Presentation] がん細胞の環境応答としてのUPRとその治療標的化 (2010)
  • Author(s): 冨田章弘
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: (大阪)
  • Year and Date: 2010-09-24
• [Presentation] がん細胞の環境応答としてのUPRとその治療標的化 (2010)
  • Author(s): 冨田章弘
  • Organizer: 日本癌学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] 小胞体ストレス下におけるUPR制御薬剤の作用機序の解析 (2010)
  • Author(s): 齋藤さかえ
  • Organizer: 日本癌学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] AP-1依存的なmiR-21の発現亢進によるがん幹細胞様SP細胞の抗がん剤耐性化 (2010)
  • Author(s): 三沢彩
  • Organizer: 日本癌学会
  • Place of Presentation: 大阪
  • Year and Date: 2010-09-24
• [Presentation] がん微小環境標的治療法の開発を目指したがん細胞のグルコース飢餓への新たな適応機構の解析 (2010)
  • Author(s): 冨田章弘、小井土大、芳賀直実、塚原里美、佐藤重男
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
  • Year and Date: 2010-09-20
• [Presentation] グルコース飢餓状態での細胞死誘導 (2010)
  • Author(s): 冨田章弘
  • Organizer: 日本CellDeath学会
  • Place of Presentation: 名古屋
  • Year and Date: 2010-07-31
• [Presentation] ミトコンドリアはグルコース飢餓環境下のがん細胞の生存を制御する (2010)
  • Author(s): 芳賀直実
  • Organizer: 日本がん分子標的治療学会
  • Place of Presentation: 東京
  • Year and Date: 2010-07-08
• [Presentation] Unfolded protein response as a therapeutic target in tumor microenvironment (2010)
  • Author(s): Tomida, A
  • Organizer: The 15th Japan ? Korea Cancer Research Workshop 2010
  • Place of Presentation: (Incheon, Korea)
• [Presentation] がん微小環境ストレスに適応したミトコンドリアDNA欠損がん細胞株の樹立とその性状解析
  • Author(s): 冨田章弘
  • Organizer: 第16回日本がん分子標的治療学会学術集会
  • Place of Presentation: 北九州
• [Presentation] がん微小環境標的治療法の開発を目指したがん細胞のグルコース飢餓への新たな適応機構の解析
  • Author(s): 冨田章弘
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] 薬剤の制がん作用と関連する遺伝子発現変動データベースの開発
  • Author(s): 冨田章弘
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Presentation] がん微小環境ストレスに適応したミトコンドリアDNA欠損がん細胞の樹立とその発現解析
  • Author(s): 冨田章弘
  • Organizer: 第71回日本癌学会学術総会
  • Place of Presentation: 札幌
• [Book] がん増殖と悪性化の分子機構、19章がんの化学療法と抗がん剤耐性 (2012)
  • Author(s): 冨田章弘(宮澤恵二・伊東進編)
  • Publisher: 化学同人
• [Book] 新臨床腫瘍学、1-5細胞死 (2012)
  • Author(s): 冨田章弘(日本臨床腫瘍学会編集)
  • Publisher: 南江堂
• [Book] がんの分子標的と治療薬、6章細胞周期・アポトーシス・ネクローシス (2010)
  • Author(s): 冨田章弘(西尾和人、西条長宏編)
  • Publisher: 羊土社
• [Remarks]
  • URL: http://www.jfcr.or.jp/chemotherapy/department/genome/index.html
• [Remarks] 公益財団法人がん研究会がん化学療法センターゲノム研究部
  • URL: http://www.jfcr.or.jp/chemotherapy/department/genome/index.html
• [Remarks]
  • URL: http://www.jfcr.or.jp/chemotherapy/department/genome/index.html
• [Remarks]
  • URL: http://www.jfcr.or.jp/chemotherapy/department/genome/index.html