ArticleThe EMBO journal2021
Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis.
Article in The EMBO journal, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 51 citations in OpenAlex.
- T cell lymphomas: cancers of aberrant immune synapse signalling.Nature reviews. Immunology · 2026Review
- Novel DAG-Lactone-Based Vav1 Inhibitors Show Anti-proliferative Activity in Pancreatic Cancer Models.ChemMedChem · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Pan-cancer analyses identify oncogenic drivers, expression signatures, and therapeutic vulnerabilities in RHO GTPase pathway genes.Frontiers in bioinformatics · 2025Article
- Deep phosphotyrosine characterisation of primary murine T cells using broad spectrum optimisation of selective triggering.Proteomics · 2024Article
- Sam68 is a druggable vulnerability point in cancer stem cells.Cancer metastasis reviews · 2024Review
- Article
- TCR Pathway Mutations in Mature T Cell Lymphomas.Journal of immunology (Baltimore, Md. : 1950) · 2023Review
- SOHO State of the Art Updates and Next Questions | New Pathways and New Targets in PTCL: Staying on Target.Clinical lymphoma, myeloma & leukemia · 2023Review
- Review
- PTCL, NOS: An update on classification, risk-stratification, and treatment.Frontiers in oncology · 2023Review
- STING pathway contributes to the prognosis of hepatocellular carcinoma and identification of prognostic gene signatures correlated to tumor microenvironment.Cancer cell international · 2022Article
- Characterization of the spectrum of trivalent VAV1-mutation-driven tumours using a gene-edited mouse model.Molecular oncology · 2022Article
- Cancer-associated mutations in VAV1 trigger variegated signaling outputs and T-cell lymphomagenesis.The EMBO journal · 2021Article
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Mutations in VAV1, a gene that encodes a multifunctional protein important for lymphocytes, are found at different frequencies in peripheral T-cell lymphoma (PTCL), non-small cell lung cancer, and other tumors. However, their pathobiological significance remains unsettled. After cataloguing 51 cancer-associated VAV1 mutations, we show here that they can be classified in five subtypes according to functional impact on the three main VAV1 signaling branches, GEF-dependent activation of RAC1, GEF-independent adaptor-like, and tumor suppressor functions. These mutations target new and previously established regulatory layers of the protein, leading to quantitative and qualitative changes in VAV1 signaling output. We also demonstrate that the most frequent VAV1 mutant subtype drives PTCL formation in mice. This process requires the concurrent engagement of two downstream signaling branches that promote the chronic activation and transformation of follicular helper T cells. Collectively, these data reveal the genetic constraints associated with the lymphomagenic potential of VAV1 mutant subsets, similarities with other PTCL driver genes, and potential therapeutic vulnerabilities.
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