Identification and characterization of mitochondrial regulators modulating the unfolded protein response

• Project/Area Number: 25430120
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: Japanese Foundation for Cancer Research
• Principal Investigator: KUNIMASA KAZUHIRO 公益財団法人がん研究会, その他部局等, 研究員 (50534020)
• Co-Investigator(Renkei-kenkyūsha): 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): 2013-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥5,330,000 (Direct Cost: ¥4,100,000、Indirect Cost: ¥1,230,000); Fiscal Year 2015: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2013: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: がん微小環境 / 小胞体ストレス応答 / グルコース飢餓 / ミトコンドリア / オートファジー / マイクロアレイ / UPR

Outline of Final Research Achievements

We focused on the unfolded protein response (UPR) that are induced by tumor microenvironmental stresses such as glucose starvation, and screened the novel UPR regulators to develop effective cancer chemotherapy under tumor microenvironment. Using a siRNA focused library and functional analyses, several candidates for the UPR modulator were identified. Furthermore, we found a novel UPR inhibitor and characterized its potential mode of action via gene expression signature- and chemosensitivity-based approaches.

Research Products

• [Journal Article] Antitumor activity of melinjo (Gnetum gnemon L.) seed extract in human and murine tumor models in vitro and in a colon-26 tumor-bearing mouse model in vivo (2015)
  • Author(s): Narayanan K. Narayanan, Kazuhiro Kunimasa, Yukio Yamori, Mari Mori, Hideki Mori, Kazuki Nakamura, George Miller, Upender Manne, Amit K. Tiwari and Bhagavathi Narayanan
  • Journal Title: Cancer Medicine Volume: 4 Issue: 11 Pages: 1767-1780
  • DOI: 10.1002/cam4.520
  • Peer Reviewed / Open Access / Int'l Joint Research
• [Journal Article] Comprehensive transcriptomic analysis of molecularly targeted drugs in cancer for target pathway evaluation (2015)
  • Author(s): Mashima T, Ushijima M, Matsuura M, Tsukahara S, Kunimasa K, Furuno A, Saito S, Kitamura M, Soma-Nagae T, Seimiya H, Dan S, Yamori T, Tomida A
  • Journal Title: Cancer Science Volume: in press Issue: 7 Pages: 909-920
  • DOI: 10.1111/cas.12682
  • Peer Reviewed / Open Access
• [Presentation] Selective cancer cell killing by spautin-1, a USP10/USP13 inhibitor, under glucose starvation (2016)
  • Author(s): Kazuhiro Kunimasa, Masaru Koido, Chika Ikeda, Satomi Tsukahara, Junko Sakurai, Shingo Dan, Takao Yamori, Akihiro Tomida
  • Organizer: AACR-JCA 10th Joint Conference
  • Place of Presentation: Maui, Hawaii, USA
  • Year and Date: 2016-02-16
  • Int'l Joint Research
• [Presentation] Selective cancer cell killing by spautin-1, a USP10/USP13 inhibitor, under glucose starvation (2015)
  • Author(s): 国政和宏、旦慎吾，矢守隆夫，冨田章弘
  • Organizer: 第74回日本癌学会学術総会
  • Place of Presentation: 名古屋
  • Year and Date: 2015-10-08
• [Presentation] Inhibitory mechanisms of spautin-1, an USP10/USP13 inhibitor, on unfolded protein response (2015)
  • Author(s): 国政和宏、旦慎吾，矢守隆夫，冨田章弘
  • Organizer: 第19回日本がん分子標的治療学会学術集会
  • Place of Presentation: 松山
  • Year and Date: 2015-06-10
• [Presentation] Selective cancer cell killing by spautin-1, an autophagy inhibitor, under glucose starvation (2014)
  • Author(s): 国政 和宏，冨田 章弘
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜
  • Year and Date: 2014-09-25 – 2014-09-27
• [Presentation] Spautin-1, an autophagy inhibitor, prevents unfolded protein response during glucose deprivation (2014)
  • Author(s): 国政 和宏，冨田 章弘
  • Organizer: 第18回日本がん分子標的治療学会学術集会
  • Place of Presentation: 仙台
  • Year and Date: 2014-06-25 – 2014-06-27