Establishment of quantitation method for proteome-based phospho-signaling pathway and its application for prediction of drug effect monitoring
Project/Area Number |
25290054
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Research Category |
Grant-in-Aid for Scientific Research (B)
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Allocation Type | Partial Multi-year Fund |
Section | 一般 |
Research Field |
Tumor diagnostics
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Research Institution | National Institutes of Biomedical Innovation, Health and Nutrition |
Principal Investigator |
Tomonaga Takeshi 国立研究開発法人医薬基盤・健康・栄養研究所, プロテオームリサーチプロジェクト, プロジェクトリーダー (80227644)
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Co-Investigator(Kenkyū-buntansha) |
ISHIHAMA Yasushi 京都大学, 薬学部, 教授 (30439244)
MATSUBARA Hisahiro 千葉大学, 医学研究院, 教授 (20282486)
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Co-Investigator(Renkei-kenkyūsha) |
NAGAYAMA Satoshi 公益財団法人がん研究会, 有明病院消化器外科, 医長 (70362499)
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Project Period (FY) |
2013-04-01 – 2016-03-31
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Project Status |
Completed (Fiscal Year 2015)
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Budget Amount *help |
¥16,770,000 (Direct Cost: ¥12,900,000、Indirect Cost: ¥3,870,000)
Fiscal Year 2015: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2014: ¥6,110,000 (Direct Cost: ¥4,700,000、Indirect Cost: ¥1,410,000)
Fiscal Year 2013: ¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
|
Keywords | リン酸化プロテオミクス / 薬効予測 / EGFR阻害剤 / 肺がん / プロテオミクス / バイオマーカー / リン酸化タンパク質 / がん / リン酸化タンパク |
Outline of Final Research Achievements |
Molecular target drugs such as kinase inhibitors for cancer treatment are not uniformly clinically effective, thus sorting the patients that will benefit from the treatments is critical. Moreover, acquired resistance for the drugs is also a critical problem. Therefore, the identification of mechanisms underlying the resistance is urgent need. Systematic quantification of kinase activation is potentially predictive of the response of kinase inhibitors and it can be quantitated by phosphorylation level of their substrates. In this study, we developed a large-scale phosphoproteome quantification method for the kinase substrates and applied for prediction of the kinase activities and drug response. We also examined the mechanism of drug resistance. By the phosphoproteome analysis of several lung cancer cell lines which are sensitive or resistant for the drug currently used in clinic, erlotinib, we identified several phosphoproteins and kinases which are able to predict drug sensitivity.
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Report
(4 results)
Research Products
(48 results)
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[Journal Article] Generation of a monoclonal antibody recognizing the CEACAM glycan structure and inhibiting adhesion using cancer tissue-originated spheroid as an antigen2016
Author(s)
Yamada K., Miyamoto Y., Tsujii A., Moriyama T., Ikuno Y., Shiromizu T., Serada S., Fujimoto M., Tomonaga T., Naka T., Yoneda Y., Oka M.
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Journal Title
Sci. Rep.
Volume: 6
Pages: 21410-21410
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Generation of a monoclonal antibody recognizing the CEACAM glycan structure and inhibiting adhesion using cancer tissue-originated spheroid as an antigen2016
Author(s)
Yamada K., Miyamoto Y., Tsujii A., Moriyama T., Ikuno Y., Shiromizu T., Serada S., Fujimoto M., Tomonaga T., Naka T., Oka M.
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Journal Title
Sci Rep
Volume: 6
Pages: 1-14
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Data for proteomic analysis of ATP-binding proteins and kinase inhibitor target proteins using an ATP probe2015
Author(s)
Adachi, J., Kishida, M., Watanabe, S., Hashimoto, Y., Fukamizu, K., and Tomonaga, T.
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Journal Title
Data in Brief
Volume: 5
Pages: 726-726
DOI
Related Report
Peer Reviewed / Open Access / Acknowledgement Compliant
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[Journal Article] Differential Proteome Analysis Identifies TGF-β-Related Pro-Metastatic Proteins in a 4T1 Murine Breast Cancer Model.2015
Author(s)
Sato, M., Matsubara, T., Adachi, J., Hashimoto, Y., Fukamizu, K., Kishida, M., Yang, Y.A., Wakefield, L.M., and Tomonaga, T
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Journal Title
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research / Acknowledgement Compliant
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[Journal Article] c-Abl induces stabilization of histone deacetylase 1 (HDAC1) in a kinase activity-dependent manner2015
Author(s)
Kazumasa Aoyama, Noritaka Yamaguchi, Ryuzaboro Yuki, Mariko Morii, Sho Kubota, Kensuke Hirata, Kohei Abe, Takuya Honda, Takahisa Kuga, Yuuki Hashimoto, Takeshi Tomonaga, and Naoto Yamaguchi
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Journal Title
Cell Biol Int
Volume: 39
Pages: 446-456
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Transcriptional dynamics of immortalized human mesenchymal stem cells during transformation.2015
Author(s)
Takeuchi, M., Higashino, A., Takeuchi, K., Hori, Y., Koshiba-Takeuchi, K., Makino, H., Monobe, Y., Kishida, M., Adachi, J., Takeuchi, J., Tomonaga, T., Umezawa, A., Kameoka, Y., and Akagi, K.
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Journal Title
PLoS ONE
Volume: 10
Pages: 0126562-0126562
DOI
NAID
Related Report
Peer Reviewed / Open Access
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[Journal Article] Discovery of colorectal cancer biomarker candidates by membrane proteomic analysis and subsequent verification using selected reaction monitoring (SRM) and tissue microarray (TMA) analysis2014
Author(s)
Kume H, Muraoka S, Kuga T, Adachi J, Narumi R, Watanabe S, Kuwano M, Kodera Y, Matsushita K, Fukuoka J, Masuda T, Ishihama Y, Matsubara H, Nomura F, Tomonaga T.
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Journal Title
Molecular and Cellular Proteomics
Volume: M113
Pages: 1471-1471
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] Lamin B2 prevents chromosome instability by ensuring proper mitotic chromosome segregation.2014
Author(s)
Kuga, T., Nie, H., Kazami, T., Satoh, M., Matsushita, K., Nomura, F., Maeshima, K., Nakayama, Y., Tomonaga, T.
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Journal Title
Oncogenesis in press.
Volume: 3
DOI
Related Report
Peer Reviewed / Acknowledgement Compliant
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[Journal Article] 3. A novel mechanism of keratin cytoskeleton organization through casein kinase Iα and FAM83H in colorectal cancer.2013
Author(s)
Kuga, T., Kume, H., Kawasaki, N., Sato, M., Adachi, J., Shiromizu, T., Hoshino, I., Nishimori, T., Matsubara, H., and Tomonaga T.
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Journal Title
J Cell Sci.
Volume: 126
Pages: 4721-31
DOI
Related Report
Peer Reviewed
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[Journal Article] Formation of long and winding nuclear F-actin bundles by nuclear c-Abl tyrosine kinase2013
Author(s)
Aoyama K., Yuki R., Horiike Y., Kubota S., Yamaguchi N., Morii M., Ishibashi K., Nakayama Y., Kuga T., Hashimoto Y., Tomonaga T, and Yamaguchi N.
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Journal Title
Experimental Cell Research
Volume: 319
Pages: 3251-3268
DOI
Related Report
Peer Reviewed
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[Journal Article] Phosphorylation of KRAB-associated protein 1 (KAP1) at Tyr-449, Tyr-458, and Tyr-517 by nuclear tyrosine kinases inhibits the association of KAP1 and heterochromatin protein 1α (HP1α) with heterochromatin.2013
Author(s)
Kubota, S., Fukumoto, Y., Aoyama, K., Ishibashi, K., Yuki, R., Morinaga, T., Honda, T., Yamaguchi, N., Hashimoto, Y., Kuga, T., Tomonaga T, and Yamaguchi, N.
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Journal Title
Journal of Biological Chemistry
Volume: 288,
Pages: 17871-17883
DOI
Related Report
Peer Reviewed
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[Presentation] Discovery and subsequent validation of biomarkers for colorectal cancer by large-scale proteomic analysis and tissue microarray analysis.2013
Author(s)
Kume H, Muraoka S, Hashimoto Y, Watanabe S, Masuda T, Ishihama Y, Fukuoka J, Kodera Y, Matsushita K, Matsubara H, Tomonaga T.
Organizer
Human Proteome Organization (HUPO) 12th annual world congress
Place of Presentation
横浜
Related Report
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[Presentation] Quantitative Phosphoproteome Analysis of Cultured Stomach Cancer Cell Lines Aimed at Development of Biomarkers for Prediction of Drug Efficacy.2013
Author(s)
Hashiguchi K, Muraoka S, Adachi J, Sato M, Kuga T, Watanabe R, Shiromizu T, Hashimoto Y, Nagano M, Kishida M, Tomonaga T.
Organizer
Human Proteome Organization (HUPO) 12th annual world congress
Place of Presentation
横浜
Related Report
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