Quantitative proteomic analysis of gastric cancer tissue reveals novel proteins in platelet-derived growth factor b signaling pathway

Oncotarget. 2017 Mar 28;8(13):22059-22075. doi: 10.18632/oncotarget.15908.

Abstract

Gastric cancer is one of the most common cancers in Asian countries. Searching for reliable biomarkers involving the development of gastric cancer is important for clinical practice. Quantitative proteomics has become an important method contributed to the discovery of novel diagnostic or therapeutic targets for the management of cancer. Here, we identified differently expressed proteins in gastric cancer and normal gastric tissues by using the high resolution mass spectrometer. Among the total of 2280 identified proteins, 87 were differentially expressed between gastric cancer and normal gastric tissues. Notably, several significant proteins are in the PDGF-B signaling pathway, including peroxiredoxin5 (PRDX5), S100A6, calreticulin (CALR) and cathepsin D (CTSD), which were validated by western blot. Furthermore, upstream regulators including PDGF-B, PDGFR-β, Akt, eIF4E and p70s6K were found significantly increased in the gastric cancer tissues. In addition, silencing of PRDX5 and PDGF-B suppressed the proliferation of gastric cancer cells in vitro. The administration of exogenous PDGF-BB recovered the reduced expression of PDGF-B signaling pathway in PDGF-B knockdown cells. Taken together, our findings suggested that PDGF-B signaling pathway plays an important role in the regulation of gastric cancer proliferation and the inhibition of this pathway may be a potential approach for treatment of gastric cancer.

Keywords: PDGF-B; PRDX5; gastric cancer; pathway; proteomic.

MeSH terms

  • Apoptosis
  • Biomarkers, Tumor / metabolism*
  • Cell Proliferation
  • Humans
  • Phosphorylation
  • Protein Interaction Maps
  • Proteome / analysis*
  • Proteomics / methods*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Proto-Oncogene Proteins c-sis / metabolism*
  • Receptor, Platelet-Derived Growth Factor beta / metabolism
  • Signal Transduction*
  • Stomach Neoplasms / metabolism*
  • Stomach Neoplasms / pathology
  • Tumor Cells, Cultured

Substances

  • Biomarkers, Tumor
  • Proteome
  • Proto-Oncogene Proteins c-sis
  • Receptor, Platelet-Derived Growth Factor beta
  • Proto-Oncogene Proteins c-akt