ArticleMolecular systems biology2023
Pan-Cancer landscape of protein activities identifies drivers of signalling dysregulation and patient survival.
Article in Molecular systems biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed.
- Article
- Unveiling unique protein and phosphorylation signatures in lung adenocarcinomas with and without ALK, EGFR, and KRAS genetic alterations.Molecular oncology · 2025Article
- Diverse oncogenes use common mechanisms to drive growth of major forms of human cancer.Science advances · 2025Article
- Infrared and Raman spectroscopy of blood plasma for rapid endometrial cancer detection.British journal of cancer · 2025Article
- Comprehensive evaluation of phosphoproteomic-based kinase activity inference.Nature communications · 2025Article
- Pan-cancer secreted proteome and skeletal muscle regulation: insight from a proteogenomic data-driven knowledge base.Functional & integrative genomics · 2025Review
- Integrative Computational Framework,bioRxiv : the preprint server for biology · 2024Article
- SignalingProfiler 2.0 a network-based approach to bridge multi-omics data to phenotypic hallmarks.NPJ systems biology and applications · 2024Article
- Predicted mechanistic impacts of human protein missense variants.bioRxiv : the preprint server for biology · 2024Article
- NB compounds are potent and efficacious FOXM1 inhibitors in high-grade serous ovarian cancer cells.Journal of ovarian research · 2024Article
- Cell cycle-dependent gene networks for cell proliferation activated by nuclear CK2α complexes.Life science alliance · 2024Article
- Gene essentiality in cancer is better predicted by mRNA abundance than by gene regulatory network-inferred activity.NAR cancer · 2023Article
- Repurposing Synthetic Congeners of a Natural Product Aurone Unveils a Lead Antitumor Agent Inhibiting Folded P-Loop Conformation of MET Receptor Tyrosine Kinase.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Gene regulatory network inference in the era of single-cell multi-omics.Nature reviews. Genetics · 2023Review
- Proteomic Characterization of Acute Myeloid Leukemia for Precision Medicine.Molecular & cellular proteomics : MCP · 2023Review
- Principles of phosphoproteomics and applications in cancer research.The Biochemical journal · 2023Article
- Pan-Cancer landscape of protein activities identifies drivers of signalling dysregulation and patient survival.Molecular systems biology · 2023Article
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Authors and funding
7 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Genetic alterations in cancer cells trigger oncogenic transformation, a process largely mediated by the dysregulation of kinase and transcription factor (TF) activities. While the mutational profiles of thousands of tumours have been extensively characterised, the measurements of protein activities have been technically limited until recently. We compiled public data of matched genomics and (phospho)proteomics measurements for 1,110 tumours and 77 cell lines that we used to estimate activity changes in 218 kinases and 292 TFs. Co-regulation of kinase and TF activities reflects previously known regulatory relationships and allows us to dissect genetic drivers of signalling changes in cancer. We find that loss-of-function mutations are not often associated with the dysregulation of downstream targets, suggesting frequent compensatory mechanisms. Finally, we identified the activities most differentially regulated in cancer subtypes and showed how these can be linked to differences in patient survival. Our results provide broad insights into the dysregulation of protein activities in cancer and their contribution to disease severity.
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