Analysis of p53/Mieap pathway in primary human cancer tissues

• Project/Area Number: 25430125
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor biology
• Research Institution: National Cancer Center Japan
• Principal Investigator: Kamino Hiroki 国立研究開発法人国立がん研究センター, 研究所, 研究員 (00625692)
• Co-Investigator(Renkei-kenkyūsha): ARAKAWA HIROFUMI 国立研究開発法人国立がん研究センター, 研究所, 分野長 (70313088) ; NAKAMURA YASUYUKI 国立研究開発法人国立がん研究センター, 研究所, 主任研究員 (90569063)
• 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: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000); Fiscal Year 2014: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2013: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
• Keywords: p53 / ミトコンドリア / 活性酸素種

Outline of Final Research Achievements

The Mieap-regulated mitochondrial quality control is inactivated in 50～70% tumors of colorectal, pancreatic, breast, gastric, and esophageal cancer patients. As the result, unhealthy mitochondria dramatically and specifically accumulated in the cancer cells in the in vivo tumor microenvironment. The cancer-specific unhealthy mitochondria produce high level of reactive oxygen species, leading to the enhanced activities of cancer migration and invasion under hypoxic conditions. These results suggest that the Mieap-regulated mitochondrial quality control has a critical role in tumor suppression in the in vivo hypoxic tumor microenvironment.

Research Products

• [Journal Article] Mieap-regulated mitochondrial quality control is frequently inactivated in human colorectal cancer. (2016)
  • Author(s): Kamino H, Nakamura Y, Tsuneki M, Sano H, Miyamoto Y, Kitamura N, Futamura M, Kanai Y, Taniguchi H, Shida D, Kanemitsu Y, Moriya Y, Yoshida K, Arakawa H.
  • Journal Title: Oncogenesis Volume: 4 Issue: 1 Pages: e181-e181
  • DOI: 10.1038/oncsis.2015.43
  • Peer Reviewed / Open Access / Acknowledgement Compliant
• [Journal Article] p53誘導性蛋白質Mieapによる新規ミトコンドリア品質管理機構 － がん抑制遺伝子p53の新しい機能 (2014)
  • Author(s): 荒川博文
  • Journal Title: 医学のあゆみ Volume: 250 Pages: 505-510
• [Presentation] Mieapは胃粘膜上皮悪性化機転を抑制する (2015)
  • Author(s): 常木雅之、中村康之、金城貴夫、荒川博文
  • 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] 消化管腫瘍の発生及び進展におけるMieap制御性ミトコンドリア品質管理機構の役割について (2014)
  • Author(s): 中村康之、喜多村憲章、安田さや香、諸田沙織、常木雅之、中西るり、荒川博文
  • Organizer: 第14回日本ミトコンドリア学会年会
  • Place of Presentation: 九州大学医学部百年講堂（博多）
  • Year and Date: 2014-12-04
• [Presentation] マウス消化管腫瘍の発生及び進展におけるMieap制御性ミトコンドリア品質管理機構の役割 (2014)
  • Author(s): 中村康之、喜多村憲章、加美野宏樹、佐野仁哉、荒川博文
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ（横浜）
  • Year and Date: 2014-09-26
• [Presentation] Mieapによって制御されるミトコンドリア品質管理機構とそのがんでの異常について (2014)
  • Author(s): 荒川博文
  • Organizer: 第73回日本癌学会学術総会
  • Place of Presentation: 横浜パシフィコ（横浜）
  • Year and Date: 2014-09-25
  • Invited
• [Presentation] Mitochondrial quality control and cancer - a new function of p53 (2014)
  • Author(s): 荒川博文
  • Organizer: ソウル大学がん研究所国際がんシンポジウム
  • Place of Presentation: 木浦（韓国）
  • Year and Date: 2014-04-17
  • Invited
• [Presentation] p53-dependent and independent functions of Mieap (2014)
  • Author(s): Yasuyuki Nakamura, Hiroki Kamino, Yuri Saito, Hitoya Sano, Hirofumi Arakawa.
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-04-07
• [Presentation] Frequent inactivation of the Mieap-regulated mitochondrial quality control in pancreatic and breast cancer (2014)
  • Author(s): Hiroki Kamino, Yasuyuki Nakamura, Hitoya Sano, Ryuya Murai, Yuri Saito, Manabu Futamura, Kazuhiro Yoshida, Nobuyuki Hiraoka, Yae Kanai, Ryoji Kushima, Toyomasa Katagiri, Hirofumi Arakawa.
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-04-06
• [Presentation] Specific role of Mieap alpha in Mieap-induced vacuole generation through an interaction with UVRAG (2014)
  • Author(s): Yasuyuki Nakamura, Hiroki Kamino, Yuri Saito, Noriaki Kitamura, Hitoya Sano, Hirofumi Arakawa.
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego (USA)
  • Year and Date: 2014-04-06
• [Presentation] Frequent inactivation of the Mieap-regulated mitochondrial quality control in colorectal cancer (2013)
  • Author(s): 加美野宏樹
  • Organizer: 第104回 米国癌研究会議
  • Place of Presentation: Washington D.C., U.S.A.
• [Presentation] Mieap, a p53-inducible protein, controls mitochondrial quality by repairing or eliminating unhealthy mitochondria (2013)
  • Author(s): 加美野宏樹
  • Organizer: Cell Symposia [Mitochondria: from Signaling to Disease]
  • Place of Presentation: Lisbon, Portugal
• [Presentation] Frequent inactivation of the Mieap-regulated mitochondrial quality control in different types of cancer (2013)
  • Author(s): 加美野宏樹
  • Organizer: がん若手研究者ワークショップ
  • Place of Presentation: 蓼科
• [Presentation] Frequent inactivation of the Mieap-regulated mitochondrial quality control in pancreatic and breast cancer (2013)
  • Author(s): 加美野宏樹
  • Organizer: 第72回 日本癌学会学術総会
  • Place of Presentation: 横浜
• [Presentation] Frequent inactivation of the Mieap-regulated mitochondrial quality control in pancreatic and breast cancer (2013)
  • Author(s): 加美野宏樹
  • Organizer: International Symposium on Mitochondria 2013
  • Place of Presentation: 東京
• [Presentation] Mieap誘導性液胞様構造物の形成におけるUVRAGとの結合を介したMieapαの役割について (2013)
  • Author(s): 加美野宏樹
  • Organizer: 第7回 オートファジー研究会
  • Place of Presentation: 静岡
• [Remarks] 国立がん研究センター研究所腫瘍生物学分野
  • URL: http://www.nccri.ncc.go.jp/s004/