Identification of molecular targets for lung adenocarcinoma treatment through proteome analysis of phospholyrated kinases

• Project/Area Number: 20390363
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Thoracic surgery
• Research Institution: Tohoku University
• Principal Investigator: SAKURADA Akira Tohoku University, 病院, 助教 (60360872)
• Co-Investigator(Kenkyū-buntansha): ENDO Chiaki 東北大学, 病院, 講師 (80333813)
• Project Period (FY): 2008 – 2010
• Project Status: Completed (Fiscal Year 2010)
• Budget Amount: ¥19,370,000 (Direct Cost: ¥14,900,000、Indirect Cost: ¥4,470,000); Fiscal Year 2010: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2009: ¥5,590,000 (Direct Cost: ¥4,300,000、Indirect Cost: ¥1,290,000); Fiscal Year 2008: ¥8,190,000 (Direct Cost: ¥6,300,000、Indirect Cost: ¥1,890,000)
• Keywords: 肺癌 / EGFR遺伝子 / キナーゼ / プロテオーム / リン酸化 / GRLF1

Research Abstract

Phospholyration of protein is important in signal transduction. We screened phospholyrated proteins in lung adenocarcinoma cell by using mass spectrometry to identify molecular targets for lung cancer treatment. Some proteins, including GFRF1/p190 A RhoGAP, were strongly controlled by EGFR protein. Functional analysis revealed that GFRF1/p190 A RhoGAP protein controls lung cancer cell proliferation through regulating MEK/ERK pathway. This protein could be a candidate of molecular treatment of lung adenocarcinoma.

Research Products

• [Journal Article] Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer. (2011)
  • Author(s): Tsao MS, Sakurada A, Ding K, Aviel-Ronen S, Ludkovski O, Liu N, Le Maitre A, Gandara D, Johnson DH, Rigas JR, Seymour L, Shepherd FA.
  • Journal Title: J Thorac Oncol Volume: 6 Pages: 139-147
  • Peer Reviewed
• [Journal Article] Prognostic and predictive value of epidermal growth factor receptor tyrosine kinase domain mutation status and gene copy number for adjuvant chemotherapy in non-small cell lung cancer. (2010)
  • Author(s): Tsao MS, Sakurada A, et al.
  • Journal Title: J Thorac Oncol 6巻 Pages: 139-147
  • Peer Reviewed
• [Journal Article] Resection of apical lung carcinoma involving the vertebral artery. (2010)
  • Author(s): Watanabe T, Okada Y, Sakurada A, Sado T, Matsuda Y, Shimizu H, Fukuhara T, Kondo T
  • Journal Title: Ann Thorac Surg Volume: 90 Pages: 302-303
  • Peer Reviewed
• [Journal Article] Phase II study of preoperative gefitinib in clinical stage I non-small-cell lung cancer. (2009)
  • Author(s): Lara-Guerra H, Sakurada A, et al.
  • Journal Title: J Clin Oncol 27巻 Pages: 6229-6236
  • Peer Reviewed
• [Journal Article] Results of long-term follow-up of photodynamic therapy for roentgenographically occult bronchogenic squamous cell carcinoma. (2009)
  • Author(s): Endo C, Sakurada A, et al.
  • Journal Title: Chest 136巻 Pages: 369-357
  • Peer Reviewed
• [Journal Article] Immunocytochemical evaluation of large cell neuroendocrine carcinoma of the lung (2009)
  • Author(s): Endo C, Sakurada A, et al.
  • Journal Title: Acta Cytol 53巻 Pages: 36-40
  • Peer Reviewed
• [Journal Article] Predictive biomarkers for EGFR therapy (2009)
  • Author(s): Sakurada A, Tsao MS
  • Journal Title: Idrugs 12巻 Pages: 34-38
  • Peer Reviewed
• [Journal Article] Phase II study of preoperative gefitinib in clinical stage I non-small-cell lung cancer. (2009)
  • Author(s): Lara-Guerra H, Waddell TK, Salvarrey MA, Joshua AM, Chung CT, Paul N, Boerner S, Sakurada A, Ludkovski O, Ma C, Squire J, Liu G, Shepherd FA, Tsao MS, Leighl NB
  • Journal Title: J Clin Oncol 27 Pages: 6229-6236
  • Peer Reviewed
• [Journal Article] Results of long-term follow-up of photodynamic therapy for roentgenographically occult bronchogenic squamous cell carcinoma. (2009)
  • Author(s): Endo C, Miyamoto A, Sakurada A, Aikawa H, Sagawa M, Sato M, Saito Y, Kondo T
  • Journal Title: Chest 136 Pages: 369-375
  • Peer Reviewed
• [Journal Article] Immunocytochemical evaluation of large cell neuroendocrine carcinoma of the lung (2009)
  • Author(s): Endo C, Honda M, Sakurada A, Sato M, Saito Y, Kondo T
  • Journal Title: Acta Cytol 53 Pages: 36-40
  • Peer Reviewed
• [Journal Article] Predictive biomarkers for EGFR therapy (2009)
  • Author(s): Sakurada A, Tsao MS
  • Journal Title: IDrugs 12 Pages: 34-38
  • Peer Reviewed
• [Journal Article] The methylation status of FBXW7 beta-form correlates with histological subtype in human thymoma. (2008)
  • Author(s): Gu Z, Mitsui H, Sakurada A, et al.
  • Journal Title: Biochem Biophys Res Commun 377巻 Pages: 685-688
  • Peer Reviewed
• [Journal Article] Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR.21. (2008)
  • Author(s): Zhu CQ, Sakurada A, et al.
  • Journal Title: J Clin Oncol 26巻 Pages: 4268-4275
  • Peer Reviewed
• [Journal Article] Phase II study of erlotinib in recurrent or metastatic endometrial cancer: NCIC IND-148. (2008)
  • Author(s): Oza AM, Sakurada A, et al.
  • Journal Title: J Clin Oncol 26巻 Pages: 4319-4325
  • Peer Reviewed
• [Journal Article] Tissue heterogeneity of EGFR mutation in lung adenocarcinoma. (2008)
  • Author(s): Sakurada A, Lara-Guerra H, et al.
  • Journal Title: J Thorac Oncol 3巻 Pages: 527-529
  • Peer Reviewed
• [Journal Article] siRNA targeting against EGFR, a promising candidate for a novel therapeutic application to lung adenocarcinoma (2008)
  • Author(s): Yamanaka S, Gu Z, Sakurada A, et al.
  • Journal Title: Pathology 75巻 Pages: 2-8
  • Peer Reviewed
• [Journal Article] The methylation status of FBXW7 beta-form correlates with histological subtype in human thymoma (2008)
  • Author(s): Gu Z, Mitsui H, lnomata K, Honda M, Endo C, Sakurada A, Sato M, Okada Y, Kondo T, Horii A
  • Journal Title: Biochem Biophys Res Commun 377 Pages: 685-688
  • Peer Reviewed
• [Journal Article] Role of KRAS and EGFR as biomarkers of response to erlotinib in National Cancer Institute of Canada Clinical Trials Group Study BR. 21 (2008)
  • Author(s): Zhu CQ, da Cunha Santos G, Ding K, Sakurada A, Cutz JC, Liu N, Zhang T, Marrano P, Whitehead M, Squire JA, Kamel-Reid S, Seymour L, Shepherd FA, Tsao MS
  • Journal Title: J Clin Oncol 26 Pages: 4268-4275
  • Peer Reviewed
• [Journal Article] Phase II study of erlotinib in recurrent or metastatic endometrial cancer : NCIC IND-148 (2008)
  • Author(s): Oza AM, Eisenhauer EA, Elit L, Cutz JC, Sakurada A, Tsao MS, Hoskins PJ, Biagi J, Ghatage P, Mazurka J, Provencher D, Dore N, Dancey J, Fyles A
  • Journal Title: J Clin Oncol 26 Pages: 4319-4325
  • Peer Reviewed
• [Journal Article] Tissue heterogeneity of EGFR mutation in lung adenocarcinoma (2008)
  • Author(s): Sakurada A, Lara-Guerra H, Liu N, Shepherd FA, Tsao MS
  • Journal Title: J Thorac Oncol 3 Pages: 527-529
  • Peer Reviewed
• [Journal Article] siRNA targeting against EGFR, a promising candidate for a novel therapeutic application to lung adenocarcinoma (2008)
  • Author(s): Yamanaka S, Gu Z, Sato M, Fujisaki R, Inomata K, Sakurada A, Inoue A, Nukiwa, T, Kondo T, Horii A
  • Journal Title: Pathobiologyl 75 Pages: 2-8
  • Peer Reviewed
• [Presentation] 肺癌細胞におけるp190-A RhoGAPの役割について (2010)
  • Author(s): 野津田泰嗣、桜田晃、遠藤千顕, ほか
  • Organizer: 日本肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-03
• [Presentation] 肺癌細胞におけるp190-A RhoGAPの役割について (2010)
  • Author(s): 野津田泰嗣、桜旦晃、江場俊介、渡邉龍秋、渡辺有為、鈴木隆哉、大石久、前田寿美子、野田雅史、佐渡哲、星川康、遠藤千顕、岡田克典、近藤丘
  • Organizer: 第51回日本肺癌学会総会
  • Place of Presentation: 広島
  • Year and Date: 2010-11-03
• [Presentation] Surgical outcome of the patients with adenoidcystic carcinoma (2010)
  • Author(s): 桜田晃, 遠藤千顕, et al.
  • Organizer: World Conference for Bronchology 2010
  • Place of Presentation: Budapest, Hungary
  • Year and Date: 2010-06-14
• [Presentation] 肺腺癌におけるリン酸化チロシンを標的とした網羅的解析(シンポジウム) (2010)
  • Author(s): 桜田晃、野津田泰嗣、遠藤千顕, ほか
  • Organizer: 日本呼吸器外科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2010-05-14
• [Presentation] 肺腺癌におけるリン酸化チロシンを標的とした網羅的解析(シンポジウム) (2010)
  • Author(s): 桜田晃、野津田泰嗣、遠藤千顕、大石久、前田寿美子、小柳津毅、野田雅史、佐渡哲、星川康、岡田克典、近藤丘
  • Organizer: 第27回日本呼吸器外科学会総会
  • Place of Presentation: 仙台
  • Year and Date: 2010-05-14
• [Presentation] Prognostic impact of visceral pleural involvement in patients with lung cancer (2009)
  • Author(s): 桜田晃, 野津田泰嗣, 遠藤千顕, et al.
  • Organizer: 13^<th> World Congress on Lung Cancer
  • Place of Presentation: San Francisco, USA
  • Year and Date: 2009-08-01
• [Remarks] ホームページ等