Global Survey of Phosphotyrosine Signaling Identifies Oncogenic Kinases in Lung Cancer

Cell. 2007 Dec 14;131(6):1190-203. doi: 10.1016/j.cell.2007.11.025.

Abstract

Despite 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 PDGFRalpha 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.

Publication types

  • Comparative Study

MeSH terms

  • Anaplastic Lymphoma Kinase
  • Carcinoma, Non-Small-Cell Lung / genetics
  • Carcinoma, Non-Small-Cell Lung / metabolism*
  • Cell Line, Tumor
  • Enzyme Activation
  • Gene Fusion
  • Humans
  • Lung Neoplasms / genetics
  • Lung Neoplasms / metabolism*
  • Models, Biological
  • Molecular Sequence Data
  • Phosphorylation
  • Phosphotyrosine / genetics
  • Phosphotyrosine / metabolism*
  • Protein-Tyrosine Kinases / genetics
  • Protein-Tyrosine Kinases / metabolism*
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor alpha / metabolism
  • Signal Transduction / genetics*

Substances

  • Phosphotyrosine
  • ALK protein, human
  • Anaplastic Lymphoma Kinase
  • Protein-Tyrosine Kinases
  • Receptor Protein-Tyrosine Kinases
  • Receptor, Platelet-Derived Growth Factor alpha

Associated data

  • GENBANK/ABX59671
  • GENBANK/ABX59672
  • GENBANK/ABX59673
  • GENBANK/ABX59674
  • GENBANK/EU236945
  • GENBANK/EU236946
  • GENBANK/EU236947
  • GENBANK/EU236948