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

2012 Fiscal Year Final Research Report

• 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
• 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 Pages: e45845
  • DOI: DOI: 10.1371/journal.pone.0045845.
  • Peer Reviewed
• [Journal Article] Hyperactivation of 4E-binding protein 1 as a mediator of biguanide-induced cytotoxicity 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 Pages: 1082-1091
  • DOI: 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: DOI: 10.1016/B978-0-12-385928-0.00018-3.
• [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 Pages: 33-40
  • DOI: 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 Pages: 1125-32
  • DOI: DOI: 10.1111/j.1349-7006.2010.01525.x.
  • Peer Reviewed
• [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)
  • Year and Date: 20101221-22
• [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
• [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