Research for new drug which targets EGFR at serine residues

• Project/Area Number: 22790639
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Single-year Grants
• Research Field: Gastroenterology
• Research Institution: Gifu University
• Principal Investigator: ADACHI Seiji 岐阜大学, 医学系研究科, 非常勤講師 (50467205)
• Project Period (FY): 2010 – 2011
• Project Status: Completed (Fiscal Year 2011)
• Budget Amount: ¥3,900,000 (Direct Cost: ¥3,000,000、Indirect Cost: ¥900,000); Fiscal Year 2011: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000); Fiscal Year 2010: ¥2,080,000 (Direct Cost: ¥1,600,000、Indirect Cost: ¥480,000)
• Keywords: EGFR / EGF / 紫外線 / p38 MAPK / セリン残基 / リン酸化 / 脱感作 / 内在化 / Ser1046/1047 / p38MAPK / UV / HSP90

Research Abstract

We have previously reported that EGCG as well as HSP90 inhibitors or anisomycin cause downregulation of the EGFR via phosphorylation at Ser1046/1047 through p38 MAPK in human cancer cells. Moreover, we demonstrated that short-wave length ultra-violet(UV-C) irradiation induces the removal of EGFR from cell surface that can protect colon cancer cells from oncogenic stimulation of EGF, resulting in cell cycle arrest. Hence, our findings suggest that EGFR at Ser1046/1047 could be a novel molecular target against human colon cancers.

Research Products

• [Journal Article] UVC irradiation suppresses platelet-derived growth factor-BB-induced migration in human pancreatic cancer cells (2012)
  • Author(s): Kawaguchi J, Adachi S, Yasuda I, Yamauchi T, Yoshioka T, Itani M, Kozawa O, Moriwaki H.
  • Journal Title: Oncol Rep Volume: 27 Pages: 935-9
  • Peer Reviewed
• [Journal Article] Use of Samples from Endoscopic, Ultrasound-Guided, 19-Gauge, Fine-Needle Aspiration in Diagnosis of Autoimmune Pancreatitis (2012)
  • Author(s): Iwashita T, Yasuda I, Doi S, Ando N, Nakashima M, Adachi S, Hirose Y, Mukai T, Iwata K, Tomita E, Itoi T, Moriwaki H.
  • Journal Title: Clin Gastroenterol Hepatol Volume: 10 Pages: 316-22
  • Peer Reviewed
• [Journal Article] Endoscopic ultrasound-guided fine needle aspiration biopsy for diagnosis of lymphoproliferative disorders : Feasibility of immunohistological, flow cytometric, and cytogenetic assessments (2012)
  • Author(s): Yasuda I, Goto N, Tsurumi H, Nakashima M, Doi S, Iwashita T, Kanemura N, Kasahara S, Adachi S, Hara T, Shimizu M, Takami T, Moriwaki H.
  • Journal Title: Am J Gastroenterol Volume: 107 Pages: 397-404
  • Peer Reviewed
• [Journal Article] UVC irradiation suppresses platelet-derived growth factor-BB-induced migration in human pancreatic cancer cells (2012)
  • Author(s): Kawaguchi J, Adachi S, et al.
  • Journal Title: Oncol Rep Volume: 27 Pages: 935-939
  • Peer Reviewed
• [Journal Article] Phosphorylation status of heat shock protein 27 plays a key role in gemcitabine-induced apoptosis of pancreatic cancer cells (2011)
  • Author(s): Nakashima M, Adachi S, Yasuda I, Yamauchi T, Kawaguchi J, Itani M, Yoshioka T, Matsushima-Nishiwaki R, Hirose Y, Kozawa O, Moriwaki H.
  • Journal Title: Cancer Lett Volume: 27 Pages: 218-25
  • Peer Reviewed
• [Journal Article] Ultraviolet enhances the sensitivity of pancreatic cancer cells to gemcitabine by activation of 5' AMP-activated protein kinase (2011)
  • Author(s): Adachi S, Yasuda I, Kawaguchi J, Yamauchi T, Nakashima M, Itani M, Nakamura M, Yoshioka T, Moriwaki H, Kozawa O.
  • Journal Title: Biochem Biophys Res Commun Volume: 414 Pages: 53-59
  • Peer Reviewed
• [Journal Article] Ultra-violet irradiation induces apoptosis via mitochondrial pathway in pancreatic cancer cells (2011)
  • Author(s): Yamauchi T, Adachi S, Yasuda I, Nakashima M, Kawaguchi J, Yoshioka T, Hirose Y, Kozawa O, Moriwaki H.
  • Journal Title: Int J Oncol Volume: 39 Pages: 1375-80
  • Peer Reviewed
• [Journal Article] Ultraviolet irradiation can induce evasion of colon cancer cells from stimulation of epidermal growth factor (2011)
  • Author(s): Adachi S, Yasuda I, Nakashima M, Yamauchi T, Kawaguchi J, Shimizu M, Itani M, Nakamura M, Nishii Y, Yoshioka T, Hirose Y, Okano Y, Moriwaki H, Kozawa O.
  • Journal Title: J Biol Chem Volume: 286 Pages: 26178-26187
  • Peer Reviewed
• [Journal Article] UV-C irradiation induces downregulation of EGF receptor via phosphorylation at serine 1046/1047 in human pancreatic cancer cells (2011)
  • Author(s): Yamauchi T, Adachi S, Yasuda I, Nakashima M, Kawaguchi J, Nishii Y, Yoshioka T, Okano Y, Hirose Y, Kozawa O, Moriwaki H.
  • Journal Title: Radiation Res Volume: 176 Pages: 565-74
  • Peer Reviewed
• [Journal Article] Inhibition of Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells (2011)
  • Author(s): Nakashima M, Adachi S, Yasuda I, Yamauchi T, Kawaguchi J, Hanamatsu T, Yoshioka T, Okano Y, Hirose Y, Kozawa O, Moriwaki H.
  • Journal Title: Mol Cancer Volume: 10 Pages: 79-79
  • Peer Reviewed
• [Journal Article] EUS-FNA of Lesions near the Aortoiliac Bifurcation via an Upper Gastrointestinal Approach (2011)
  • Author(s): Doi S, Yasuda I, Nakashima M, Kawaguchi J, Yamauchi T, Iwashita T, Toda K, Adachi S, Shimizu M, Tsurumi H, Moriwaki H.
  • Journal Title: J Gastroenterol Hepatol Volume: 26 Pages: 1717-20
  • Peer Reviewed
• [Journal Article] Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases (2011)
  • Author(s): Shimizu M, Adachi S, Masuda M, Kozawa O, Moriwaki H.
  • Journal Title: Mol Nutr Food Res Volume: 55 Pages: 832-43
  • Peer Reviewed
• [Journal Article] Chemoprevention of Head and Neck Cancer by Green Tea Extract : EGCG-The Role of EGFR Signaling and"Lipid Raft" (2011)
  • Author(s): Masuda M, Wakasaki T, Toh S, Shimizu M, Adachi S.
  • Journal Title: J Oncol Volume: 540148 Pages: 1-7
  • Peer Reviewed
• [Journal Article] Rho-kinase inhibitor upregulates migration by altering focal adhesion formation via the Akt pathway in colon cancer cells (2011)
  • Author(s): Adachi S, Yasuda I, Nakashima M, Yamauchi T, Yoshioka T, Okano Y, Moriwaki H, Kozawa O.
  • Journal Title: Eur J Pharmacol Volume: 650 Pages: 145-150
  • Peer Reviewed
• [Journal Article] Ultraviolet irradiation can induce evasion of colon cancer cells from stimulation of epidermal growth factor (2011)
  • Author(s): Adachi S, et al.
  • Journal Title: J Biol Cbem Volume: 286 Pages: 26178-26187
  • Peer Reviewed
• [Journal Article] Rho-associated coiled-coil containing protein kinase enhances the activation of epidermal growth factor receptor in pancreatic cancer cells (2011)
  • Author(s): Nakashima M, Adachi S, et al.
  • Journal Title: Mol Cancer Volume: 10 Pages: 79-79
  • Peer Reviewed
• [Journal Article] Cancer chemoprevention with green tea catechins by targeting receptor tyrosine kinases (2011)
  • Author(s): Shimizu M, Adachi S, et al.
  • Journal Title: Mol Nutr Food Res Volume: 55 Pages: 832-843
  • Peer Reviewed
• [Journal Article] UV-C irradiation induces downregulation of EGF receptor via phosphorylation at serine 1046/1047 in human pancreatic cancer cells (2011)
  • Author(s): Yamauchi T, Adachi S, et al.
  • Journal Title: Radiation Res Volume: 176 Pages: 565-574
  • Peer Reviewed
• [Journal Article] Ultra-violet irradiation induces apoptosis via mitochondrial pathway in pancreatic cancer cells (2011)
  • Author(s): Yamauchi T, Adachi S, et al.
  • Journal Title: Int J Oncol Volume: 39 Pages: 1375-1380
  • Peer Reviewed
• [Journal Article] Phosphorylation status of heat shock protein 27 plays a key role in gemcitabine-induced apoptosis of pancreatic cancer cells (2011)
  • Author(s): Nakashima M, Adachi S, et al.
  • Journal Title: Cancer Lett Volume: 27 Pages: 218-225
  • Peer Reviewed
• [Journal Article] Synergistic growth inhibition in HL-60 cells by the combination of acyclic retinoid and vitamin K2 (2010)
  • Author(s): Kitagawa J, Hara T, Tsurumi H, Ninomiya S, Ogawa K, Adachi S, Kanemura N, Kasahara S, Shimizu M, Moriwaki H.
  • Journal Title: J Cancer Res Clin Oncol Volume: 137 Pages: 779-787
  • Peer Reviewed
• [Journal Article] (-)-Epigallocatechin gallate inhibits growth and activation of the VEGF/VEGFR axis in human colorectal cancer cells (2010)
  • Author(s): Shimizu M, Shirakami Y, Sakai H, Yasuda Y, Kubota M, Adachi S, Tsurumi H, Hara Y, Moriwaki H.
  • Journal Title: Chem Biol Interact Volume: 14 Pages: 247-52
  • Peer Reviewed
• [Journal Article] HSP90 inhibitors induce down-regulation of EGF receptor via p38 MAPK-mediated phosphorylation at Ser1046/7 in human pancreatic cancer cells (2010)
  • Author(s): Adachi S, Yasuda I, Nakashima M, Yamauchi T, Moriwaki H, Kozawa O.
  • Journal Title: Oncol Rep Volume: 23 Pages: 1709-14
  • Peer Reviewed
• [Journal Article] Rho-kinase regulates negatively the epidermal growth factor-stimulated colon cancer cell proliferation (2010)
  • Author(s): Nakashima M, Adachi S, Yasuda I, Yamauchi T, Kozawa O, Moriwaki H.
  • Journal Title: Int J Oncol Volume: 36 Pages: 585-92
  • Peer Reviewed
• [Journal Article] HSP90 inhibitors induce down-regulation of EGF receptor via p38 MAPK-mediated phosphorylation at Ser1046/7 in human pancreatic cancer cells (2010)
  • Author(s): Adachi S, et al.
  • Journal Title: Oncol Rep Volume: 23 Pages: 1709-1714
  • Peer Reviewed
• [Journal Article] Rho-kinase regulates negatively the epidermal growth factor-stimulated colon cancer cell proliferation (2010)
  • Author(s): Nakashima M, Adachi S, et al.
  • Journal Title: Int J Oncol Volume: 36 Pages: 585-592
  • Peer Reviewed
• [Presentation] ROCK/Rho-kinaseによる大腸がんの抑制機能について～新規治療標的の可能性 (2011)
  • Author(s): 足立政治, 等
  • Organizer: 第53回消化器病学会大会
  • Place of Presentation: 福岡
  • Year and Date: 2011-10-22
• [Presentation] パネルディスカッション10消化器疾患における分子標的治療; ROCK/Rho-kinaseによる大腸がんの抑制機能について～新規治療標的の可能性～ (2011)
  • Author(s): 足立政治、森脇久隆、小澤修
  • Organizer: JDDW2011(第53回消化器病学会大会)
  • Place of Presentation: 福岡
• [Presentation] 膵がんの細胞増殖能におけるRho-kinaseの役割 (2011)
  • Author(s): 足立政治、中島賢憲、安田一朗、山内貴裕、河口順二、森脇久隆、小澤修
  • Organizer: 第42回日本膵臓学会総会
  • Place of Presentation: 弘前
• [Presentation] 膵がん細胞に対する短波長紫外線(UV-C)照射の腫瘍増殖抑制効果の検討 (2011)
  • Author(s): 山内貴裕、足立政治、安田一朗、中島賢憲、河口順二、小澤修、森脇久隆
  • Organizer: 第42回日本膵臓学会総会
  • Place of Presentation: 弘前
• [Presentation] 膵がん細胞に対する短波長紫外線のアポトーシス誘導効果についての検討 (2011)
  • Author(s): 河口順二、足立政治、山内貴裕、安田一朗、中島賢憲、小澤修、森脇久隆
  • Organizer: 第42回日本膵臓学会総会
  • Place of Presentation: 弘前
• [Presentation] Heat shock protein 90阻害剤の膵がん治療への応用 (2010)
  • Author(s): 足立政治、安田一朗、中島賢憲、山内貴裕、森脇久隆、小澤修
  • Organizer: 2010JDDW日本消化器病学会大会
  • Place of Presentation: 横浜
  • Year and Date: 2010-10-13
• [Presentation] Heat shock protein 90 inhibitors as a possible new candidate for the treatment of human pancreatic cancer (2010)
  • Author(s): Seiji Adachi, Ichiro Yasuda, Masanori Nakashima, Takahiro Yamauchi, Hisataka Moriwaki and Osamu Kozawa
  • Organizer: Joint Meeting of the International Association of Pancreatology and the Japan Pancreas Society 2010 JPS Symposium 2
  • Place of Presentation: Fukuoka
  • Year and Date: 2010-07-11
• [Presentation] Phosphorylation of epidermal growth factor receptor at Ser1046/1047 by p38 mitogen-activated protein kinase plays a critical role in its downregulation in cancer cells (2010)
  • Author(s): Seiji Adachi, Masanori Nakashima, Takahiro Yamauchi, Yohei Shirakami, Masahito Shimizu, Ichiro Yasuda, Hisataka Moriwaki and Osamu Kozawa
  • Organizer: 101^<th> AACR(American Association for Cancer Research) Annual Meeting
  • Place of Presentation: Washington DC
  • Year and Date: 2010-04-21
• [Presentation] Phosphorylation of epidermal growth factor receptor at Ser1046/1047 by p38 mitogen-activated protein kinase plays a critical role in its downregulation in cancercells (2010)
  • Author(s): Adachi S, et al.
  • Organizer: アメリカ癌学会総会
  • Place of Presentation: アメリカ・ワシントンCD
  • Year and Date: 2010-04-19