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| Status |
Public on Sep 21, 2018 |
| Title |
Vav proteins maintain epithelial traits in breast cancer cells using miR-200c-dependent and independent mechanisms |
| Platform organism |
synthetic construct |
| Sample organism |
Mus musculus |
| Experiment type |
Non-coding RNA profiling by array
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| Summary |
Here, we report that the Rho GTPase activators Vav2 and Vav3 utilize a new, miR-200c-dependent mechanism that maintains the epithelial state by limiting the abundance of the Zeb2 transcriptional repressor in breast cancer cells. In parallel, Vav proteins engage an expression program that maintains epithelial cell traits in 3D culture.
Depletion of Vav proteins triggers EMT in epithelioid breast cancer cells and, conversely, expression of constitutively active Vav2 restores both miR-200c expression and epithelial traits in mesenchymal breast cancer cells. In silico analyses suggest that the negative Vav-Zeb2 axis is operative in human luminal breast tumors.
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| Overall design |
4T1 cells were transduced with empty pLKO lentiviral vector (3 replicates included) and lentiviral shRNAs to Vav2 and Vav3 transcripts (2 independent experiments, 3 replicates each). Knockdown cells were then rescued by reexpressing either Vav2 (3 replicates) or Vav3 (3 replicates).
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| Contributor(s) |
Lorenzo-Martín LF, Citterio C, Menacho-Márquez M, Larive RM, García-Escudero R, Robles-Valero J, Cuadrado M, Fernández-Pisonero MI, Dosil M, Sevilla MA, Montero MJ, Fernández-Salguero PM, Paramio JM, Bustelo XR |
| Citation(s) |
30087437 |
| Submission date |
Apr 04, 2017 |
| Last update date |
Jan 02, 2019 |
| 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)
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| Lab |
Laboratory of Stem Cell Bioengineering
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| Street address |
EPFL – SV – IBI – LSCB – Station 15
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| City |
Lausanne |
| State/province |
Vaud |
| ZIP/Postal code |
1015 |
| Country |
Switzerland |
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| Platforms (1) |
| GPL8786 |
[miRNA-1] Affymetrix Multispecies miRNA-1 Array |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA381602 |
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