Comparison of SYK Signaling Networks Reveals the Potential Molecular Determinants of Its Tumor-Promoting and Suppressing Functions.
Marion BuffardAurélien NaldiGilles FreissMarcel DeckertOvidiu RadulescuPeter J CoopmanRomain Maxime LarivePublished in: Biomolecules (2021)
Spleen tyrosine kinase (SYK) can behave as an oncogene or a tumor suppressor, depending on the cell and tissue type. As pharmacological SYK inhibitors are currently evaluated in clinical trials, it is important to gain more information on the molecular mechanisms underpinning these opposite roles. To this aim, we reconstructed and compared its signaling networks using phosphoproteomic data from breast cancer and Burkitt lymphoma cell lines where SYK behaves as a tumor suppressor and promoter. Bioinformatic analyses allowed for unveiling the main differences in signaling pathways, network topology and signal propagation from SYK to its potential effectors. In breast cancer cells, the SYK target-enriched signaling pathways included intercellular adhesion and Hippo signaling components that are often linked to tumor suppression. In Burkitt lymphoma cells, the SYK target-enriched signaling pathways included molecules that could play a role in SYK pro-oncogenic function in B-cell lymphomas. Several protein interactions were profoundly rewired in the breast cancer network compared with the Burkitt lymphoma network. These data demonstrate that proteomic profiling combined with mathematical network modeling allows untangling complex pathway interplays and revealing difficult to discern interactions among the SYK pathways that positively and negatively affect tumor formation and progression.
Keyphrases
- tyrosine kinase
- epidermal growth factor receptor
- signaling pathway
- clinical trial
- induced apoptosis
- diffuse large b cell lymphoma
- breast cancer cells
- stem cells
- transcription factor
- dna methylation
- big data
- mesenchymal stem cells
- pi k akt
- gene expression
- randomized controlled trial
- risk assessment
- endoplasmic reticulum stress
- pseudomonas aeruginosa
- staphylococcus aureus
- health information
- young adults
- amino acid
- climate change
- candida albicans
- artificial intelligence
- breast cancer risk