Analysis of common molecular mechanisms and pharmaceutical research in cancer invasion and angiogenesis

• Project/Area Number: 20590293
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: General medical chemistry
• Research Institution: Osaka Bioscience Institute
• Principal Investigator: HASHIMOTO Ari Osaka Bioscience Institute, 大学院・医学研究科, 助教 (60390803)
• Research Collaborator: 京都大学, 医学部 ; オックスフォード大学, Weatherall Institute of Molecular Medicine Cell Signalling
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥4,810,000 (Direct Cost: ¥3,700,000、Indirect Cost: ¥1,110,000); Fiscal Year 2010: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2009: ¥1,300,000 (Direct Cost: ¥1,000,000、Indirect Cost: ¥300,000); Fiscal Year 2008: ¥2,210,000 (Direct Cost: ¥1,700,000、Indirect Cost: ¥510,000)
• Keywords: 血管新生 / 癌浸潤 / Arf6 / AMAP1 / ArfGEF / 乳癌 / チロシンリン酸化 / 乳腺

Research Abstract

We have shown that GEP100 links EGFR signaling to Arf6 activation to induce invasive activities of some breast cancer cells. Our analyses demonstrate that the same GEP100-Arf6-AMAP1 pathway is essential for VEGF-induced angiogenesis activities, and that VEGFR2, via phospho-Tyr951, binds to the PH domain of GEP100 to activate the Arf6-AMAP1 pathway to induce angiogenesis. Moreover, we found the small compound that inhibits the interaction between GEP100 and VEGFR-2. The GEP100-Arf6-AMAP1 pathway, activated by receptor tyrosine kinases, appears to be common in angiogenesis and cancer invasion, and provide their new therapeutic targets from a pathological analysis.

Research Products

• [Journal Article] The EGFR-GEP100-Arf6-AMAP1 signaling pathway specific to breast cancer invasion and metastasis. (2009)
  • Author(s): Sabe, H., Hashimoto, S., Morishige, M., Hashimoto, A., Ogawa, E., Nam, J.M, Miura, K., Yano, H., Onodera, Y.
  • Journal Title: Traffic 10 Pages: 982-993
  • Peer Reviewed
• [Journal Article] The EGFR-GEP100-Arf6-AMAP1 signaling pathway specific to breast cancer invasion and metastasis (2009)
  • Author(s): H.Sabe, S.Hashimoto, M.Morishige, E.Ogawa, A.Hashimoto, J.-M.Nam, K.Miura, H.Yano, Y.Onodera
  • Journal Title: Traffic 10 Pages: 982-993
  • Peer Reviewed
• [Journal Article] The EGFR-GEP100-Arf6 pathway in breast cancer : Full invasiveness is not from the inside. (2008)
  • Author(s): Sabe, H., Hashimoto, S., Morishige, M., Hashimoto, A., Ogawa, E.
  • Journal Title: Cell Adhesion & Migration. 103 Pages: 7036-7041
  • Peer Reviewed
• [Journal Article] GEP100 links EGFR signaling to Arf6 activation to induce breast cancer invasion. (2008)
  • Author(s): Morishige , M., Hashimoto, S., Ogawa, E., Toda, Y., Kotani, H., Hirose, M., Wei, S., Hashimoto, A., Yamada, A., Yano, H., Mazaki, Y., Kodama, H., Nio, Y., Manabe, Y., Wada, H., Kobayashi, H., ^*Sabe, H.
  • Journal Title: Nat Cell Biol. 10 Pages: 85-92
  • Peer Reviewed
• [Journal Article] The EGFR-GEP100-Arf6 pathway in breast cancer : Full invasiveness is not from the inside (2008)
  • Author(s): H. Sabe, S. Hashimoto, M. Morishige, A. Hashimoto, E. Ogawa
  • Journal Title: Cell Adhesion & Migration 2 Pages: 71-73
  • Peer Reviewed
• [Journal Article] The EGFR-GEP100-Arf6-AMAP1 signaling pathway specific to breast cancer invasion and metastasis
  • Author(s): H. Sabe, S. Hashimoto, M. Morishige, E. Ogawa, A. Hashimoto, J.-M. Nam, K. Miura, H. Yano Y. Onodera
  • Journal Title: Traffic (掲載確定)
  • Peer Reviewed
• [Presentation] TGFβ1 activates GEP100-Arf6-AMAP1 pathway to induce EMT, and possible relationship of this activation to cancer stemness (2010)
  • Author(s): 橋本あり
  • 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: ポスター発表 神戸
  • Year and Date: 2010-12-08
• [Presentation] TGFβ1 activates GEP100-Arf6-AMAP1 pathway to induce EMT, and possible relationship of this activation to cancer stemness (2010)
  • Author(s): 橋本あり
  • 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: 神戸ボートアイランド(神戸市)
  • Year and Date: 2010-12-08
• [Presentation] HGFR-mediated activation of GEP100-Arf6-AMAP1 pathway is an integral part for TGFβ-induced cancerous EMT and invasiveness (2010)
  • Author(s): 橋本あり
  • Place of Presentation: 口頭発表 大阪
  • Year and Date: 2010-09-23
• [Presentation] HGFR-mediated activation of GEP100-Arf6-AMAP1 pathway is an integral part for TGFβ-induced cancerous EMT and invasiveness (2010)
  • Author(s): 橋本あり
  • Organizer: 第69回日本癌学会学術総会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-09-23
• [Presentation] GEP100-Arf6-AMAP1 pathway is activated by VEGFR2 and promotes vascular remodeling and VE-cadherin endocytosis in endothelial cells (2010)
  • Author(s): 橋本あり
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: ポスター発表 大阪
  • Year and Date: 2010-05-19
• [Presentation] GEP100-Arf6-AMAP1 pathway is activated by VEGFR2 and promotes vascular remodelin and VE-cadherin endocytosis in endothelial cells (2010)
  • Author(s): 橋本あり
  • Organizer: 第62回日本細胞生物学会大会
  • Place of Presentation: 大阪国際会議場(大阪市)
  • Year and Date: 2010-05-19
• [Presentation] 腫瘍血管における透過性亢進に関与する分子輸送のメカニズム及び病態の解明 (2009)
  • Author(s): 橋本あり
  • Organizer: 細胞内ロジスティックス斑会議
  • Place of Presentation: 口頭発表 沖縄
  • Year and Date: 2009-11-11
• [Presentation] 腫瘍血管における透過性亢進に関与する分子輸送のメカニズム及び病態の解明 (2009)
  • Author(s): 橋本あり
  • Organizer: 細胞内ロジスティックス斑会議
  • Place of Presentation: 万座ビーチリゾート会議場(恩納村)
  • Year and Date: 2009-11-11
• [Presentation] GEP100-Arf6-AMAP1-cortactin シグナル経路は癌浸潤と血管新生に共通である (2008)
  • Author(s): 橋本あり
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会)
  • Place of Presentation: シンポジウム口頭発表 神戸
  • Year and Date: 2008-12-12
• [Presentation] GEP100-Arf6-AMAP1-cortactin シグナル経路は癌浸潤と血管新生に共通である (2008)
  • Author(s): 橋本あり
  • Organizer: BMB2008(第31回日本分子生物学会年会・第81回日本生化学会大会 合同大会)
  • Place of Presentation: シンポジウム:蛋白質のリン酸化と細胞応答
  • Year and Date: 2008-12-12
• [Presentation] Common usage of the GEP100-Arf6-AMAP1 pathway in tumor invasion, angiogenesis and vascular permeability (2008)
  • Author(s): 橋本あり
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: ワークショップ口頭発表 名古屋
  • Year and Date: 2008-10-30
• [Presentation] Common usage of the GEP100-Arf6-AMAP1 pathway in tumor invasion, angiogenesis and vascular permeability (2008)
  • Author(s): 橋本あり
  • Organizer: 第67回日本癌学会学術総会
  • Place of Presentation: Workshop : 10-7 Regulation of angiogenesis
  • Year and Date: 2008-10-30
• [Presentation] Common usage of the GEP100-Arf6-AMAP1 pathway in tumor invasion, angiogenesis and vascular permeability (2008)
  • Author(s): 橋本あり
  • Organizer: 第20回欧州癌研究治療機関・米国国立ガン研究所・米国ガン学会合同シンポジウム『分子標的とがん治療』
  • Place of Presentation: ポスター発表 ジュネーブ・スイス
  • Year and Date: 2008-10-22
• [Presentation] Common usage of the GEP100-Arf6-AMAP1 pathway in tumor invasion, angiogenesis and vascular permeability (2008)
  • Author(s): 橋本あり
  • Organizer: 第20回 欧州癌研究治療機関・米国国立ガン研究所・米国ガン学会合同シンポジウム『分子標的とがん治療』
  • Place of Presentation: Poster session
  • Year and Date: 2008-10-22
• [Presentation] Common usage of the GEP100-Arf6 signaling pathway in tumor invasion, angiogenesis, and vascular permeability (2008)
  • Author(s): 橋本あり
  • Organizer: Second JCA-AACR Special Joint Conference
  • Place of Presentation: ポスター発表 淡路
  • Year and Date: 2008-07-15
• [Presentation] Common usage of the GEP100-Arf6 signaling pathway in tumor invasion, angiogenesis, and vascular permeability (2008)
  • Author(s): 橋本あり
  • Organizer: Second JCA-AACR Special Joint Conference
  • Place of Presentation: Poster session
  • Year and Date: 2008-07-15
• [Presentation] Common usage of an Arf6-GEP100 signaling pathway in angiogenesis and tumor invasion (2008)
  • Author(s): 橋本あり
  • Organizer: ワークショップ
  • Place of Presentation: 口頭発表 横浜
  • Year and Date: 2008-07-01
• [Presentation] Common usage of an Arf6-GEP100 signaling pathway in angiogenesis and tumor (2008)
  • Author(s): 橋本あり
  • Organizer: 第60回 日本細胞生物学会
  • Place of Presentation: Workshop :癌浸潤転移における細胞運動のメカニズム
  • Year and Date: 2008-07-01
• [Book] (2008)がんの浸潤形質獲得過程における低分子量Gタンパク質Arf6シグナル伝達(実験医学増刊号)(vol.26(15)) (2008)
  • Author(s): 橋本茂、森重真毅、小川栄治、橋本あり、小野寺康仁、佐邊壽孝
  • Publisher: 羊土社
• [Book] 実験医学増刊号 (2008)
  • Author(s): 橋本茂, 森重真毅, 小川栄治, 橋本あり, 小野寺康仁, 佐邊壽孝
  • Total Pages: 7
  • Publisher: 羊土社
• [Remarks] ホームページ等
• [Remarks]
  • URL: http://www.sabelab.jp/