Mechanism of EBV-mediated gastric carcinogenesis depending on TLR3 signals

• Project/Area Number: 23590909
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Gastroenterology
• Research Institution: Hokkaido University
• Principal Investigator: IWAKIRI Dai 北海道大学, 遺伝子病制御研究所, 助教 (10307853)
• Project Period (FY): 2011 – 2013
• Project Status: Completed (Fiscal Year 2013)
• Budget Amount: ¥5,200,000 (Direct Cost: ¥4,000,000、Indirect Cost: ¥1,200,000); Fiscal Year 2013: ¥1,430,000 (Direct Cost: ¥1,100,000、Indirect Cost: ¥330,000); Fiscal Year 2012: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000); Fiscal Year 2011: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: EBウイルス / 胃がん / EBER / TLR3 / LMP2A / EBV / 自然免疫 / anoikis

Research Abstract

We have demonstrated that EBV-encoded small RNA (EBER) is released by EBV-infected gastric cancer cells and released EBER triggers the signaling from toll-like receptor 3, a sensor of viral RNA. Further study indicated that EBER-mediated activation of TLR3 signals led to the growth promotion of EBV-infected gastric cancer cells, suggesting that EBER contribute to gastric carcinogenesis through TLR3 activation. We also demonstrated that latent membrane protein 2A (LMP2A) confers anoikis resistance to EBV-infected epithelial cells, leading to epithelial malignancy.

Research Products

• [Journal Article] EBウイルス感染と胃発癌 (2014)
  • Author(s): 岩切大
  • Journal Title: 日本臨床増刊号「最新胃癌学」 Volume: 72 Pages: 58-61
• [Journal Article] Epstein-Barr virus latent membrane 2A contributes to anoikis resitance through ERK activation (2013)
  • Author(s): Iwakiri, D., Minanitani, T., Samanta, M
  • Journal Title: J. VIrol Volume: 87 Pages: 8227-8234
  • Peer Reviewed
• [Journal Article] Epstein-Barr virus latent membrane protein 2A contributes to anoikis resistance through ERK activation (2013)
  • Author(s): Iwakiri D, Minamitani T, Samanta M
  • Journal Title: J Virol Volume: 87 (14) Issue: 14 Pages: 8227-8234
  • DOI: 10.1128/jvi.01089-13
  • Peer Reviewed
• [Journal Article] EBウイルス感染と胃発癌 (2013)
  • Author(s): 岩切 大
  • Journal Title: 日本臨床増刊号 「 最新胃癌学 」 Volume: 72 Pages: 58-61
• [Journal Article] A novel animal model of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice (2011)
  • Author(s): Sato, K., Misawa, N., Nie, C., Satou, Y., Iwakiri, D., Matsuoka, M., Takahashi, R., Kuzushima, K., Ito, M., Takada, K., Koyanagi, Y.
  • Journal Title: Blood Volume: 117 Pages: 5663-5673
  • Peer Reviewed
• [Journal Article] Adenovirus virus-associated RNAs induce type I interferon expression through a RIG-I-mediated pathway (2011)
  • Author(s): Minamitani, T., Iwakiri, D., Takada, K.
  • Journal Title: J.Virol Volume: 85 Pages: 4035-4040
  • Peer Reviewed
• [Journal Article] Adenovirus virus-associated RNAs induce type I interferon expression a RIG-I-mediated pathway (2011)
  • Author(s): Minamitani, T., Iwakiri, D., Takada, K.
  • Journal Title: J.Virol Volume: 85 Issue: 8 Pages: 4035-4040
  • DOI: 10.1128/jvi.02160-10
  • Peer Reviewed
• [Journal Article] A novel animal model of Epstein-Barr virus-associated hemophagocytic lymphohistiocytosis in humanized mice (2011)
  • Author(s): Sato K, Misawa N, Nie C, Satou Y, Iwakiri D, Matsuoka M, Takahashi R, Kuzushima K, Ito M, Takada K, Koyanagi Y
  • Journal Title: Blood Volume: 117 Issue: 21 Pages: 5663-5673
  • DOI: 10.1182/blood-2010-09-305979
  • Peer Reviewed
• [Presentation] EBウイルスによる発癌の分子機構 (2013)
  • Author(s): 岩切大
  • Organizer: 第61回日本ウイルス学会学術集会シンポジウム
  • Place of Presentation: 神戸国際会議場, 神戸
  • Year and Date: 2013-11-10
• [Presentation] EBウイルスによる自然免疫シグナル修飾と発癌がん (2012)
  • Author(s): 岩切大
  • Organizer: 共同利用・共同研究拠点研究集会, 感染と癌・感染癌のエフェクター分子とその標的
  • Place of Presentation: 北海道大学, 札幌
  • Year and Date: 2012-09-18
• [Presentation] Exosomal transfer of EBER contributes to gastric cancer development (2012)
  • Author(s): Iwakiri, D,. Minamitani, T.
  • Organizer: The 15th biennial conference of International association of EBV-associated disease
  • Place of Presentation: Sheraton hotel Philadelphia Philadelphia
  • Year and Date: 2012-08-03
• [Presentation] Exosomal transfer of EBER contributes to gastric cancer development. (2012)
  • Author(s): Iwakiri D, Minamitani T.
  • Organizer: The 15th biennial conference of International association of EBV-associated disease
  • Place of Presentation: Sheraton hotel Philadelphia, Philadelphia, USA
• [Presentation] EBウイルスによる自然免疫シグナル修飾と発がん (2012)
  • Author(s): 岩切 大
  • Organizer: 共同利用・共同研究拠点 研究集会 感染と癌・感染癌のエフェクター分子とその標的
  • Place of Presentation: 北海道大学 札幌
• [Presentation] EBV-encoded small RNA is secreted via exosomes in gastric epithelial cells (2011)
  • Author(s): Iwakiri, D., Minamitani, T., Takada, K.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場, 名古屋(English oral session)
  • Year and Date: 2011-10-04
• [Presentation] EBV-encoded small RNA is secreted via exosomes in gastric epithelial cells. (2011)
  • Author(s): Iwakiri D., Takada K.
  • Organizer: 第70回日本癌学会学術総会
  • Place of Presentation: 名古屋国際会議場(名古屋市)
• [Presentation] EBウイルスによる発癌の分子機構
  • Author(s): 岩切 大
  • Organizer: 第61回日本ウイルス学会学術集会シンポジウム「発がんウイルス」
  • Place of Presentation: 神戸国際会議場 神戸市