Role of DENN domain proteins in the development of neuroblastoma cancer stem cells.

• Project/Area Number: 26860801
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Pediatrics
• Research Institution: Kobe University
• Principal Investigator: Yamamoto Nobuyuki 神戸大学, 医学部附属病院, 助教 (20596043)
• Research Collaborator: Nishimura Noriyuki 神戸大学, 大学院, 特命教授 (00322719) ; Hayakawa Akira 神戸大学, 大学院, 准教授 (40379376) ; Kosaka Yoshiyuki 兵庫県立こども病院, 血液腫瘍科, 部長 ; Yanai Tomoko 兵庫県立こども病院, 血液腫瘍科, 医長
• Project Period (FY): 2014-04-01 – 2016-03-31
• Project Status: Completed (Fiscal Year 2015)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2015: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000); Fiscal Year 2014: ¥1,950,000 (Direct Cost: ¥1,500,000、Indirect Cost: ¥450,000)
• Keywords: 神経芽腫 / 細胞内小胞輸送 / 低分子量G蛋白質 / DENNドメイン蛋白質 / Rabファミリー低分子量G蛋白質 / がん幹細胞

Outline of Final Research Achievements

More than half of high-risk neuroblastoma patients experience tumor relapses and less than 40% can expect a long-term survival. Intracellular vesicle transport seems to play an important role on the development of neuroblastoma cancer stem cells that are responsible for tumor relapses. In this study, we focused on DENN domain proteins, regulators of intracellular vesicle transport, and revealed that a member of DENN domain proteins is involved in the progression of neuroblastoma.

Research Products

• [Journal Article] Involvement of aldehyde dehydrogenase 1A2 in the regulation of cancer stem cell properties in neuroblastoma. (2015)
  • Author(s): Hartomo TB, Pham TVH, Yamamoto N, Hirase S, Hasegawa D, Kosaka Y, Matsuo M, Hayakawa A, Takeshima Y, Iijima K, Nishio H, and Nishimura N.
  • Journal Title: Int J Oncol Volume: 46 Issue: 3 Pages: 1089-1098
  • DOI: 10.3892/ijo.2014.2801
  • Peer Reviewed
• [Journal Article] Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients. (2015)
  • Author(s): Yamamoto N, Kozaki A, Hartomo TB, Yanai T, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Hirase S, Mori T, Hayakawa A, Iijima K, Nishio H, and Nishimura N.
  • Journal Title: Oncol Let Volume: 10 Issue: 5 Pages: 3228-3232
  • DOI: 10.3892/ol.2015.3710
  • Peer Reviewed
• [Presentation] DENN domain protein DENND2A regulates the progression of neuroblastoma (2016)
  • Author(s): Nobuyuki Yamamoto, Khin Kyaemon Thwin, Jun-ya Fujimura, Keita Nakanishi, Takeshi Mori, Akira Hayakawa, Hisahide Nishio, Masafumi Matsuo, Dai-ichiro Hasegawa, Kei-ichiro Kawasaki, Yoshiyuki Kosaka, Kazumoto Iijima, Noriyuki Nishimura
  • Organizer: Advance in Neuroblastoma Research Conference
  • Place of Presentation: Cairns Convention Centre, Cairns, Australia
  • Year and Date: 2016-06-20
  • Int'l Joint Research
• [Presentation] DENN domain protein DENND2A mediates the progression of neuroblastoma (2015)
  • Author(s): Yamamoto N, Horinouchi T, Fujimura J, Mori T, Hayakawa A, Hasegawa D, Kosaka Y, Nishio H, Iijima K, and Nishimura N.
  • Organizer: 第57回日本小児血液がん学会
  • Place of Presentation: 甲府富士屋ホテル
  • Year and Date: 2015-11-27
• [Presentation] Differential expression of minimal residual disease markers in peripheral blood and bone marrow samples from high-risk neuroblastoma patients. (2015)
  • Author(s): Uemura S, Yamamoto N, Kozaki A, Nino N, Takafuji S, Yokoi T, Saito A, Ishida T, Hasegawa D, Kawasaki K, Kosaka Y, Mori T, Hayakawa A, Iijima K, Nishio H, and Nishimura N.
  • Organizer: 第57回日本小児血液がん学会
  • Place of Presentation: 甲府富士屋ホテル
  • Year and Date: 2015-11-27
• [Presentation] Involvement of DENN domain protein DENND2A in the progression of neuroblastoma (2015)
  • Author(s): Nobuyuki Yamamoto, Daiichiro Hasegawa, and Noriyuki Nishimura
  • Organizer: 第74回日本癌学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] 神経芽腫の発症・進展におけるRab6BとRab28の役割. (2015)
  • Author(s): 西村範行, 山本暢之, 長谷川大一郎.
  • Organizer: 第74回日本癌学会
  • Place of Presentation: 名古屋国際会議場
  • Year and Date: 2015-10-08
• [Presentation] Neuroblastoma minimal residual disease markers are differentially expressed in peripheral blood and bone marrow samples. (2015)
  • Author(s): Uemura S, Yamamoto N, Kozaki A, Yanai T, Hasegawa D, Kawasaki K, Kosaka Y, Hayakawa A, Iijima K, Nishio H, and Nishimura N.
  • Organizer: 11th Asian Society for Pediatric Research
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2015-04-15
  • Int'l Joint Research
• [Presentation] 神経芽腫がん幹細胞の発生・分化における細胞内小胞輸送の制御因子Rab6Bの役割. (2014)
  • Author(s): 西村範行, Thi Van Huyen Pham, Tri Budi Hartomo, 山本暢之, 平瀬敏志, 早川晶, 矢内友子, 長谷川大一郎, 川崎圭一郎, 小阪嘉之, 松尾雅文, 飯島一誠, 西尾久英.
  • Organizer: 第56回日本小児血液・がん学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] Aldehyde dehydrogenase ALDH1A2 regulates cancer stem cell properties in neuroblastoma. (2014)
  • Author(s): Nishimura N, Hartomo TB, Pham TVH, Yamamoto N, Hirase S, Hayakawa A, Yanai T, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Iijima K, Nishio H.
  • Organizer: 第56回日本小児血液・がん学会学術集会
  • Place of Presentation: 岡山
  • Year and Date: 2014-11-28 – 2014-11-30
• [Presentation] Aldehyde dehydrogenase 1A2 expression correlates with cancer stem cell properties in neuroblastoma (2014)
  • Author(s): Nishimura N, Hartomo TB, Pham TVH, Yamamoto N, Hirase S, Hayakawa A, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Takeshima Y, Iijima K, and Nishio H.
  • Organizer: Advances in Neuroblastoma Research Conference 2014
  • Place of Presentation: Cologne, Germany
  • Year and Date: 2014-05-13 – 2014-05-16
• [Presentation] Induction of ALDH1A2 expression is critical for cancer stem cell properties in neuroblastoma. (2014)
  • Author(s): Nishimura N, Hartomo TB, Pham TVH, Yamamoto N, Hirase S, Hayakawa A, Hasegawa D, Kawasaki K, Kosaka Y, Matsuo M, Takeshima Y, Iijima K, and Nishio H.
  • Organizer: AACR Annual Meeting 2014
  • Place of Presentation: San Diego, CA, USA
  • Year and Date: 2014-04-05 – 2014-04-09