2013 Fiscal Year Final Research Report
Discovery of predictive biomarkers for molecular target drug effectiveness of advanced colorectal cancer using phosphoproteomics
| Project/Area Number |
24659622
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| Research Category |
Grant-in-Aid for Challenging Exploratory Research
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| Allocation Type | Single-year Grants |
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| Research Field |
Digestive surgery
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| Research Institution | 独立行政法人医薬基盤研究所 |
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Principal Investigator |
TOMONAGA Takeshi 独立行政法人医薬基盤研究所, 創薬基盤研究部, プロジェクトリーダー (80227644)
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| Project Period (FY) |
2012-04-01 – 2014-03-31
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| Keywords | リン酸化プロテオミクス / 分子標的薬 / バイオマーカー / 薬効予測 / 大腸癌 |
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| Research Abstract |
For practice of personalized medicine, prediction of molecular target drug effectiveness and selection of sensitive patients to the drug are needed. Effect of drug depends on the activity of growth signals in which the drug is involved. Protein phosphorylation plays a crucial role for the activity of growth signals.
We aimed at establishment of comprehensive quantitation method for phosphoproteins and discovery of predictive biomarkers for molecular target drug effectiveness of advanced colorectal cancer using the method. We modified previous phosphoproteomics technologies and succeeded in identification of 30000 phosphopeptides in one experiment. This is the largest study of phosphoproteomics identification to date. We also showed that activity of PDPK1 kinase, a kinase downstream of EGFR signaling pathway, might be involved in sensitivity of an anti-EGFR antibody drug Cetuximab.
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[Journal Article] Discovery of colorectal cancer biomarker candidates by membrane proteomic analysis and subsequent verification using selected reaction monitoring and tissue microarray 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., and Tomonaga T
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Journal Title
Mol Cell Proteomics
Volume: (in press)
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[Journal Article] Selective evaluation of high density lipoprotein from mouse small intestines by an in situ perfusion technique2014
Author(s)
Y amaguchi S., Zhang B., Tomonaga T, Seino U., Kanagawa A., Segawa M., Nagasaka H., Suzuki A., Miida T., Yamada S., Sasaguri Y., Doi T., Saku K., Okazaki M., Tochino Y., and Hirano K
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Journal Title
J Lipid Res
Volume: (in press)
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[Journal Article] A novel mechanism of keratin cytoskeleton organization through casein kinase I alpha and FAM83H in colorectal cancer2013
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
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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
Exp Cell Res
Volume: 319
Pages: 3251-68
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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 1alpha (HP1alpha) with Heterochromatin2013
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
J Biol Chem
Volume: 288
Pages: 17871-17883
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[Journal Article] In-depth Membrane Proteomic Study of Breast Cancer Tissues for the Generation of a Chromosome-based Protein List2013
Author(s)
Muraoka, S., Kume, H., Adachi, J., Shiromizu, T., Watanabe, S., Masuda, T., Ishihama, Y., and Tomonaga T
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Journal Title
J Proteome Res
Volume: 12
Pages: 208-213
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[Journal Article] Identification of Missing Proteins in the neXtProt Database and Unregistered Phosphopeptides in the PhosphoSitePlus Database As Part of the Chromosome-Centric Human Proteome Project2013
Author(s)
Shiromizu, T., Adachi, J., Watanabe, S., Murakami, T., Kuga, T., Muraoka, S., and Tomonaga T
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Journal Title
J Proteome Res
Volume: 12
Pages: 2414-2421
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[Journal Article] A strategy for SRM-based verification of biomarker candidates discovered by iTRAQ method in limited breast cancer tissue samples2012
Author(s)
Muraoka S, Kume H, Watanabe S, Adachi J, Kuwano M, Sato M, Kawasaki N, Kodera Y, Ishitobi M, Inaji H, Miyamoto Y, Kato K, Tomonaga T
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Journal Title
J Proteome Res
Volume: 11
Pages: 4201-4210
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[Journal Article] A Strategy for Large-Scale Phosphoproteomics and SRM-Based Validation of Human Breast Cancer Tissue Samples2012
Author(s)
Narumi R, Murakami T, Kuga T, Adachi J, Shiromizu T, Muraoka S, Kume H, Kodera Y, Matsumoto M, Nakayama K, Miyamoto Y, Ishitobi M, Inaji H, Kato K, Tomonaga T
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Journal Title
J Proteome Res
Volume: 11
Pages: 5311-5322
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[Presentation] Discovery and subsequent validation of biomarkers for colorectal cancer by large-scale proteomic analysis and tissue microarray analysis2013
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) 12^<th> Annual World Congress
Place of Presentation
Yokohama, Japan
Year and Date
20130914-18
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[Presentation] Development of High-throughput Screening System Using Autoantibody Library for Discovery of Scirrhous Gastric Cancer Biomarker2013
Author(s)
Muraoka S, Kume H, Saitoh H, Enomoto Y, Ito Y, Nishizuka S, Wakabayashi G, Hoshino I, Matsubara H, and Tomonaga T
Organizer
Human Proteome Organization (HUPO) 12^<th> Annual World Congress
Place of Presentation
Yokohama, Japan
Year and Date
20130914-18
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[Presentation] Quantitative Phosphoproteome Analysis of Cultured Stomach Cancer Cell Lines Aimed at Development of Biomarkers for Prediction of Drug Efficacy2013
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) 12^<th> annual world congress
Place of Presentation
Yokohama, Japan
Year and Date
20130914-18
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[Presentation] Phosphorylation dynamics in an early response of DNA damage signaling2012
Author(s)
Adachi J, Kuga T, Shiromizu T, Kume H, Muraoka S, Hashiguchi K, Narumi R, Watanabe S, Kuwano M, Matsumoto M, Nakayama KI, Ikura M, Ikura T, Takata M Tomonaga T
Organizer
HUPO2012 11^<th> World Congress
Place of Presentation
Boston, U.S.A.
Year and Date
20120909-13
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[Presentation] A strategy for SRM-based systematic validation of biomarker candidates discovered by iTRAQ method in breast cancer tissue samples2012
Author(s)
Muraoka S, Kume H, Watanabe S, Kuwano M, Sato M, Kawasaki N, Adachi J, Ishitobi M, Inaji H, Miyamoto Y, Kato K, Kodera Y, Tomonaga T
Organizer
HUPO2012 11^<th> World Congress
Place of Presentation
Boston, USA
Year and Date
20120909-13
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