Expression of CagA in polarized epithelial cells elicits forced mitogenesis

• Project/Area Number: 21790412
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Bacteriology (including Mycology)
• Research Institution: The University of Tokyo
• Principal Investigator: KAMIYA Naoko The University of Tokyo, 大学院・医学系研究科, 助教 (40279352)
• Project Period (FY): 2009 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,290,000 (Direct Cost: ¥3,300,000、Indirect Cost: ¥990,000); Fiscal Year 2010: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000); Fiscal Year 2009: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: ヘリコバクター・ピロリ / 胃がん / cagA遺伝子 / 上皮細胞極性 / 細胞増殖 / 胃癌

Research Abstract

Infection with Helicobacter pylori cagA-positive strains is associated with gastric carcinoma. CagA-deregulated SHP2 elicits sustained Erk-MAPK activation. CagA also interacts and inhibits PAR1, resulting in induction of junctional and polarity defects. In polarized epithelial cells, CagA-driven Erk-MAPK signal prevents p21 expression by activating RhoA, thereby inducing forced mitogenesis.

Research Products

• [Journal Article] Pathophysiological functions of the CagA oncoprotein during infection by Helicobacter pylori. (2011)
  • Author(s): N. Murata-Kamimya.
  • Journal Title: Microbes Infect. 印刷中(掲載確定)
  • Peer Reviewed
• [Journal Article] Pathophysiological functions of the CagA oncoprotein during infection by Helicobacter pylori (2011)
  • Author(s): Murata-Kamiya, N.
  • Journal Title: Microbes and Infection Volume: (掲載確定(印刷中))
  • Peer Reviewed
• [Journal Article] Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21. (2010)
  • Author(s): Y. Saito, N. Murata-Kamiya, Y. Ohba, T. Hirayama, M. Hatakeyama.
  • Journal Title: J.Exp.Med. 207 Pages: 2157-2174
  • Peer Reviewed
• [Journal Article] 胃癌発症におけるピロリ菌癌タンパク質CagAの役割 (2010)
  • Author(s): 紙谷尚子、畠山昌則
  • Journal Title: 細胞工学 29巻6号 Pages: 554-560
• [Journal Article] Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein. (2010)
  • Author(s): N. Murata-Kamiya, K. Kikuchi, T. Hayashi, H. Higashi, M. Hatakeyama.
  • Journal Title: Cell Host Microbe 7 Pages: 399-411
  • Peer Reviewed
• [Journal Article] Helicobacter pylori exploits host membrane phosphatidylserine for delivery, localization, and pathophysiological action of the CagA oncoprotein (2010)
  • Author(s): Murata-Kamiya, N.
  • Journal Title: Cell Host & Microbe Volume: 7 Pages: 399-411
  • Peer Reviewed
• [Journal Article] Conversion of Helicobacter pylori CagA from senescence inducer to oncogenic driver through polarity-dependent regulation of p21 (2010)
  • Author(s): Saito, Y.
  • Journal Title: The Journal of Experimental Medicine Volume: 207 Pages: 2157-2174
  • Peer Reviewed
• [Journal Article] 胃癌発症におけるピロリ菌癌タンパク質CagAの往割 (2010)
  • Author(s): 紙谷尚子
  • Journal Title: 細胞工学 Volume: 129 Pages: 554-560
• [Journal Article] Role of PAR1/MARK kinases in the morphogenetic activity of Helicobacter pylori CagA. (2009)
  • Author(s): H. Lu, N. Murata-Kamiya, Y. Saito, M. Hatakeyama.
  • Journal Title: J.Biol.Chem. 284 Pages: 23024-23036
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA causes mitotic impairment and induces chromosomal instability. (2009)
  • Author(s): M. Umeda, N. Murata-Kamiya, Y. Saito, Y. Ohba, M. Takahashi, M. Hatakeyama.
  • Journal Title: J.Bio.Chem. 284 Pages: 22166-22172
  • Peer Reviewed
• [Journal Article] Helicobacter pylori CagA causes mitotic impairment and induces chromosomal instability (2009)
  • Author(s): Umeda, M.
  • Journal Title: The Journal of Biological Chemistry 284 Pages: 22166-22172
  • Peer Reviewed
• [Journal Article] Role of PAR1/MARK kinases in the morphogenetic activity of Helicobacter pylori CagA (2009)
  • Author(s): Lu, H.
  • Journal Title: The Journal of Biological Chemistry 284 Pages: 23024-23036
  • Peer Reviewed
• [Presentation] Helicobacter pylori CagA utilizes host membrane phosphatidylserine to invade and deregulate gastric epithelial cells (2010)
  • Author(s): 紙谷尚子
  • Organizer: The 15th Japan-Korea Cancer Research Workshop
  • Place of Presentation: Sheraton Inchon Hotel (Inchon, Korea)
  • Year and Date: 2010-12-22
• [Presentation] Helicobacter pyloriがんタンパク質CagAと宿主細胞膜ホスファチジルセリンの相互作用 (2010)
  • Author(s): 紙谷尚子、菊地健司、林剛瑠、東秀明、畠山昌則
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会合同大会
  • Place of Presentation: 神戸ポートピアホテル(兵庫県)
  • Year and Date: 2010-12-10
• [Presentation] Interaction of Helicobacter pylori oncoprotein CagA with host membrane phosphatidylserine (2010)
  • Author(s): 紙谷尚子
  • Organizer: 第33回日本分子生物学会年会・第83回日本生化学会大会 合同大会
  • Place of Presentation: 神戸ポートピアホテル(兵庫県神戸市)
  • Year and Date: 2010-12-10
• [Presentation] ヘリコバクター・ピロリは細胞膜ホスファチジルセリンを利用して宿主細胞にCagA癌タンパク質を注入する (2010)
  • Author(s): 紙谷尚子、菊地健司、林剛瑠、東秀明、畠山昌則
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] PHelicobacter pylori CagAによる上皮細胞極性依存的な細胞増殖の亢進 (2010)
  • Author(s): 齊藤康弘、紙谷尚子、畠山昌則
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] SHP-2もしくはPAR1と結合できないCagAを発現する遺伝子組み換えヘリコバクターピロリ菌の病態生理学的な検討 (2010)
  • Author(s): 菊地健司、紙谷尚子、近藤哲、畠山昌則
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] GEF-H1は細胞極性制御因子PAR1b/MARK2の下流分子として機能する (2010)
  • Author(s): 山橋幸恵、齊藤康弘、紙谷尚子、畠山昌則
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪府)
  • Year and Date: 2010-09-22
• [Presentation] Helicobacter pylori exploits host membrane phosphatidylserine for delivery of the CagA oncoprotein (2010)
  • Author(s): 紙谷尚子
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: リーガロイヤルホテル大阪(大阪府大阪市)
  • Year and Date: 2010-09-22
• [Presentation] 胃がん発症におけるヘリコバクター・ピロリCagAの意義 (2009)
  • Author(s): 紙谷尚子、畠山昌則
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-02
• [Presentation] Helicobacter pylori CagAは上皮細胞極性を利用し異常細胞増殖を誘導する (2009)
  • Author(s): 齊藤康弘、紙谷尚子、大場雄介、畠山昌則
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-01
• [Presentation] Epstein-Barrウィルスによる上皮細胞の発癌の初期変化 (2009)
  • Author(s): 吉山裕規、紙谷尚子、高田賢蔵、畠山昌則
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜(神奈川県)
  • Year and Date: 2009-10-01
• [Presentation] Role of Helicobacter pylori CagA in the gastric carcinogenesis (2009)
  • Author(s): Kamiya, N.
  • Organizer: 第68回日本癌学会学術総会
  • Place of Presentation: パシフィコ横浜神奈川県