Global survey of phosphotyrosine signaling identifies oncogenic kinases in lung cancer
Autor: | Jon M. Kornhauser, Joan MacNeill, Jin Yuan, Roberto D. Polakiewicz, Qingfu Zeng, John Rush, Anthony Possemato, Zhi-Ping Tan, Julie Nardone, Daiqiang Li, Herbert Haack, Xinmin Zhou, Jeffrey Mitchell, Michael J. Comb, Matthew P. Stokes, Bradley L. Smith, Jian Min Ren, Cynthia Reeves, Jian Yu, Laura Sullivan, Ting-Lei Gu, Corey E. Bakalarski, Ailan Guo, Klarisa Rikova, Kimberly Lee, Judit Villén, Yerong Hu, Randy Wetzel, Steven P. Gygi, Yu Li |
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Rok vydání: | 2007 |
Předmět: |
Lung Neoplasms
Receptor Platelet-Derived Growth Factor alpha PROTEINS Receptor Protein-Tyrosine Kinases Molecular Sequence Data HUMDISEASE Models Biological General Biochemistry Genetics and Molecular Biology Receptor tyrosine kinase Carcinoma Non-Small-Cell Lung Cell Line Tumor medicine ROS1 Anaplastic lymphoma kinase Humans Anaplastic Lymphoma Kinase Phosphorylation Phosphotyrosine biology Biochemistry Genetics and Molecular Biology(all) Cancer JAK-STAT signaling pathway Protein-Tyrosine Kinases medicine.disease Lorlatinib Cell biology Enzyme Activation SIGNALING biology.protein Gene Fusion Tyrosine kinase Signal Transduction |
Zdroj: | Cell. 131(6) |
ISSN: | 0092-8674 |
Popis: | SummaryDespite the success of tyrosine kinase-based cancer therapeutics, for most solid tumors the tyrosine kinases that drive disease remain unknown, limiting our ability to identify drug targets and predict response. Here we present the first large-scale survey of tyrosine kinase activity in lung cancer. Using a phosphoproteomic approach, we characterize tyrosine kinase signaling across 41 non-small cell lung cancer (NSCLC) cell lines and over 150 NSCLC tumors. Profiles of phosphotyrosine signaling are generated and analyzed to identify known oncogenic kinases such as EGFR and c-Met as well as novel ALK and ROS fusion proteins. Other activated tyrosine kinases such as PDGFRα and DDR1 not previously implicated in the genesis of NSCLC are also identified. By focusing on activated cell circuitry, the approach outlined here provides insight into cancer biology not available at the chromosomal and transcriptional levels and can be applied broadly across all human cancers. |
Databáze: | OpenAIRE |
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