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| Status |
Public on Sep 01, 2021 |
| Title |
Cancer-associated mutations in VAV1 trigger variegated signaling outputs and drive T cell lymphomagenesis |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by array
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| Summary |
Mutations in VAV1, a multifunctional signaling protein essential for T lymphocytes, have been recently found in peripheral T cell lymphoma (PTCL) and other tumors. However, their pathobiological significance remains unsettled.
Here, we show that these mutations belong to several subclasses according to the spectra of VAV1 signaling branches deregulated by them. These mutations target both known and new regulatory hotspots as well as transitional activation states of the protein. The most frequent VAV1 mutant subclass drives PTCL formation in mice by exacerbating normal VAV1- dependent signaling responses in follicular helper T cells.
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| Overall design |
CD4+ T cells expressing either GFP or oncogenic Vav1 were introduced in immunocompromised mice and analyzed 6 months later.
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| Contributor(s) |
Robles-Valero J, Fernández-Nevado L, Lorenzo-Martín LF, Cuadrado M, Fernández-Pisonero I, Rodríguez-Fdez S, Astorga-Simón EN, Abad A, Caloto R, Martín-Zanca D, Mallo M, Bustelo XR |
| Citation(s) |
34617326 |
| Submission date |
Jan 17, 2021 |
| Last update date |
Dec 01, 2021 |
| Contact name |
L. Francisco Lorenzo-Martín |
| E-mail(s) |
luis.lorenzomartin@epfl.ch
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| Organization name |
École Polytechnique Fédérale de Lausanne (EPFL)
|
| Lab |
Laboratory of Stem Cell Bioengineering
|
| Street address |
EPFL – SV – IBI – LSCB – Station 15
|
| City |
Lausanne |
| State/province |
Vaud |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL23038 |
[Clariom_S_Mouse] Affymetrix Clariom S Assay, Mouse (Includes Pico Assay) |
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| Samples (10)
|
| GSM5024406 |
CD4+ T cells expressing GFP (spleen) rep1 |
| GSM5024407 |
CD4+ T cells expressing GFP (spleen) rep2 |
| GSM5024408 |
CD4+ T cells expressing oncogenic Vav1 (spleen) rep1 |
| GSM5024409 |
CD4+ T cells expressing oncogenic Vav1 (spleen) rep2 |
| GSM5024410 |
CD4+ T cells expressing oncogenic Vav1 (spleen) rep3 |
| GSM5024411 |
CD4+ T cells expressing oncogenic Vav1 (spleen) rep4 |
| GSM5024412 |
CD4+ T cells expressing GFP (lymph node) rep1 |
| GSM5024413 |
CD4+ T cells expressing GFP (lymph node) rep2 |
| GSM5024414 |
CD4+ T cells expressing oncogenic Vav1 (lymph node) rep1 |
| GSM5024415 |
CD4+ T cells expressing oncogenic Vav1 (lymph node) rep2 |
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| Relations |
| BioProject |
PRJNA692770 |
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