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Quantitative Mass Spectrometric Profiling of Cancer-cell Proteomes Derived From Liquid and Solid Tumors
Published on: February 27, 2015
[Analysis of oncogenic signaling induced by tyrosine kinases in tumors by SILAC-based quantitative proteomic
Audrey Sirvent1, Serge Urbach2, Serge Roche1
1CNRS UMR5237, université de Montpellier 1 et 2, centre de recherche de biochimie macromoléculaire (CRBM), 34000 Montpellier, France.
Abstract:
Protein tyrosine kinases (TK) transmit intracellular signaling induced by many extracellular stimuli resulting in cell growth or adhesion. Deregulation of their activity leads to malignant cell transformation that plays an important role in human cancer. The signaling pathways involved in this oncogenic process are however only partially elucidated. Interestingly, SILAC-based quantitative proteomics allow the identification of the whole spectrum of TK substrates and the dynamic of phosphorylation state involved in oncogenic signaling. For example, this approach has highlighted the unsuspected complexity of the oncogenic signaling induced by the TK Src in colorectal cancer (CRC) cells. In this review, we describe a new SILAC-based technology applied to in vivo models of human tumors engrafted in nude mice. This method revealed significant differences between Src-oncogenic signaling of CRC cells in tumors and in culture. Finally, we discuss the interest of SILAC with recently described in vivo proteomic methods and in cancer, including the analysis of oncogenic signaling in tumor progression and the anti-tumoral activity of TK inhibitors in vivo.
Insights
Quantitative proteomics using SILAC reveals complex oncogenic signaling pathways in cancer. This technology, applied in vivo, identified key differences in tumor signaling compared to cell cultures, aiding cancer research.
Area of Science:
- Biochemistry and Molecular Biology
- Cancer Biology
- Proteomics
Context:
- Protein tyrosine kinases (TK) are crucial for cell signaling, and their dysregulation drives cancer.
- Understanding TK-mediated oncogenic signaling pathways is vital for cancer treatment.
- Current knowledge of these pathways remains incomplete.
Purpose:
- To review the application of SILAC-based quantitative proteomics for identifying TK substrates and phosphorylation dynamics.
- To introduce a novel SILAC technology for analyzing in vivo tumor models.
- To highlight differences in oncogenic signaling between cancer cells in vitro and in vivo.
Summary:
- SILAC (Stable Isotope Labeling by Amino acids in Quantitative Proteome) enables comprehensive identification of TK substrates and phosphorylation changes.
- A new SILAC-based method applied to human tumor xenografts in nude mice revealed distinct Src-oncogenic signaling patterns.
- Significant discrepancies were observed between Src-oncogenic signaling in colorectal cancer cells cultured in vitro versus within tumors.
Impact:
- This approach advances the understanding of oncogenic signaling in tumor progression.
- It facilitates the analysis of anti-tumoral activity of TK inhibitors in vivo.
- Provides a powerful tool for dissecting complex signaling networks in cancer research.
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