The identification of targeting molecules for EMT-activating signals from ErbB family receptor in lung cancer

• Project/Area Number: 26462125
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Respiratory surgery
• Research Institution: Kyoto University
• Principal Investigator: MENJU Toshi 京都大学, 医学研究科, 特定病院助教 (30527081)
• Co-Investigator(Kenkyū-buntansha): 園部 誠 京都大学, 医学研究科, 准教授 (00432378)
• Research Collaborator: SABE Hisataka 北海道大学, 大学院・医学研究科・分子生物学教室, 教授
• Project Period (FY): 2014-04-01 – 2017-03-31
• Project Status: Completed (Fiscal Year 2016)
• Budget Amount: ¥4,940,000 (Direct Cost: ¥3,800,000、Indirect Cost: ¥1,140,000); Fiscal Year 2016: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2015: ¥1,170,000 (Direct Cost: ¥900,000、Indirect Cost: ¥270,000); Fiscal Year 2014: ¥2,600,000 (Direct Cost: ¥2,000,000、Indirect Cost: ¥600,000)
• Keywords: 肺癌 / EMT / 浸潤転移 / Arf6 / GEP100 / EGFR / Grb2 / アダプター分子

Outline of Final Research Achievements

We revealed the enhancing mechanisms of Arf6 pathway via the binding between activated EGFR and GEP100. Grb2 overexpression induces the promotion of the binding of these molecules and its downstream molecule, Arf6 invasion pathway, leading the activation of EMT and in vitro invasive activity in lung cancer cells.
Furthermore, mutant Grb2 overexpression which does not bind EGFR did not show the enhancement of Arf6 pathway. These results possibly showed the inhibition of the binding among these molecular complex is the promising targets to suppress the invasive activity in lung cancer cells

Research Products

• [Journal Article] UCHL1 provides diagnostic and antimetastatic strategies due to its deubiquitinating effect on HIF-1alpha (2015)
  • Author(s): Goto Y, Zeng L, YeomCJ, Zhu Y, Morinibu A, Shinoyam K, Kobayashi M, Hirota K, Itasaka S, Yoshimura M, Tanimoto K, Sowa T, Menju T, Sonobe M, Kakeya H, Toi M, Date H, Hammond EM, Hiraoka M, Harada H.
  • Journal Title: Nat Commun Volume: 6 Issue: 1 Pages: 1-10
  • DOI: 10.1038/ncomms7153
  • Peer Reviewed / Open Access
• [Journal Article] Genes suppressed by DNA methylation in non-small cell lung cancer reveal the epigenetics of epithelial-mesenchymal transition. (2014)
  • Author(s): Lin SH, Wang J, Saintigny P, Wu CC, Giri U, Zhang J, Menju T, Diao L, Byers L, Weinstein JN, Coombes KR, Girard L, Komaki R, Wistuba II, Date H, Minna JD, Heymach JV.
  • Journal Title: BMC Genomics Volume: Dec 8;15 Issue: 1 Pages: 1079-1079
  • DOI: 10.1186/1471-2164-15-1079
  • Peer Reviewed / Open Access
• [Journal Article] Indentification of subsets of patients with favorable prognosis after recurrence in completely resected non-small cell lung cancer. (2014)
  • Author(s): 335.Sonobe M, Yamada T, Sato M, Menju T, Aoyama A, Sato T, Chen F, Omasa M, Bando T, Date H.
  • Journal Title: Ann Surg Oncol Volume: 21(8) Pages: 2546-54
  • Peer Reviewed / Open Access
• [Presentation] GEP100-Arf6 pathway enhanced by Grb2 expression plays important roles for node-metastasis and EMT activation of lung cancer (2016)
  • Author(s): 毛受 暁史
  • Organizer: 第２４回ヨーロッパ癌学会
  • Place of Presentation: マンチェスター、UK
  • Year and Date: 2016-07-09
  • Int'l Joint Research
• [Presentation] GEP100-Arf6経路におけるGrb2アダプター分子の意義 (2016)
  • Author(s): 毛受 暁史
  • Organizer: 第３３回日本呼吸器外科学会総会
  • Place of Presentation: 京都市、日本
  • Year and Date: 2016-05-12
• [Presentation] GEP100-Arf6 pathway enhanced by Grb2 expression plays important roles for node-metastasis of lung cancer (2016)
  • Author(s): 毛受 暁史
  • Organizer: アメリカ癌学会
  • Place of Presentation: ニューオーリンズ、USA
  • Year and Date: 2016-04-16
  • Int'l Joint Research
• [Presentation] Grb2 promotes cancer invasiveness via EGF-induced GEP100-Arf6 pathway Grb2はEGF刺激によるGEP100-Arf6経路活性化を介した腫瘍浸潤転移能を促進する (2015)
  • Author(s): Toshi Menju, Naoto Imamura, Shinya Neri, Hiroyuki Cho, Takao Nakanishi, Kei Shikuma, Terumasa Sowa, Makoto Sonobe, Hisataka Sabe, Hiroshi Date
  • Organizer: 第１８回欧州癌治療学会
  • Place of Presentation: ウィーン、オーストリア
  • Year and Date: 2015-09-25
  • Int'l Joint Research
• [Presentation] Clinicopathological analysis on EMT activation in lung adenocarcinoma 肺腺癌切除検体におけるEMT活性化に伴う臨床病理学的解析 (2015)
  • Author(s): Toshi Menju, Terumasa Sowa, Shinya Neri, Takao Nakanishi, Hiroyuki Cho, Kei Shikuma, Kyoko Hijiya, Hideki Motoyama, Akihiro Aoyama, Fengshi Chen, Makoto Sonobe, Toshihiko Sato, Mitsugu Oomasa, *Akihiko Yoshizawa, *Hironori Haga, Hiroshi Date
  • Organizer: 第１６回世界肺癌学会総会
  • Place of Presentation: デンバー、コロラド州、USA
  • Year and Date: 2015-09-05
  • Int'l Joint Research
• [Remarks] 京都大学呼吸器外科
  • URL: http://www.thoracic-kyoto-u.gr.jp