| Added by | pcoopman |
|---|---|
| Group name | EquipePC |
| Item Type | Journal Article |
| Title | Vav proteins maintain epithelial traits in breast cancer cells using miR-200c-dependent and independent mechanisms |
| Creator | Lorenzo-Martín et al. |
| Author | L. Francisco Lorenzo-Martín |
| Author | Carmen Citterio |
| Author | Mauricio Menacho-Márquez |
| Author | Javier Conde |
| Author | Romain M. Larive |
| Author | Sonia Rodríguez-Fdez |
| Author | Ramón García-Escudero |
| Author | Javier Robles-Valero |
| Author | Myriam Cuadrado |
| Author | Isabel Fernández-Pisonero |
| Author | Mercedes Dosil |
| Author | María A. Sevilla |
| Author | María J. Montero |
| Author | Pedro M. Fernández-Salguero |
| Author | Jesús M. Paramio |
| Author | Xosé R. Bustelo |
| Abstract | The bidirectional regulation of epithelial-mesenchymal transitions (EMT) is key in tumorigenesis. Rho GTPases regulate this process via canonical pathways that impinge on the stability of cell-to-cell contacts, cytoskeletal dynamics, and cell invasiveness. Here, we report that the Rho GTPase activators Vav2 and Vav3 utilize a new Rac1-dependent and 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 a mir-200c-independent expression prometastatic program that maintains epithelial cell traits only under 3D culture conditions. Consistent with this, the depletion of endogenous Vav proteins triggers mesenchymal features in epithelioid breast cancer cells. Conversely, the ectopic expression of an active version of Vav2 promotes mesenchymal-epithelial transitions using E-cadherin-dependent and independent mechanisms depending on the mesenchymal breast cancer cell line used. In silico analyses suggest that the negative Vav anti-EMT pathway is operative in luminal breast tumors. Gene signatures from the Vav-associated proepithelial and prometastatic programs have prognostic value in breast cancer patients. |
| Publication | Oncogene |
| Volume | 38 |
| Issue | 2 |
| Pages | 209-227 |
| Date | 2019-01 |
| Journal Abbr | Oncogene |
| Language | eng |
| DOI | 10.1038/s41388-018-0433-7 |
| ISSN | 1476-5594 |
| Library Catalog | PubMed |
| Extra | PMID: 30087437 PMCID: PMC6230471 |
| Tags | Animals, Breast Neoplasms, Cell Line, Tumor, Epithelial-Mesenchymal Transition, Female, Gene Expression Regulation, Neoplastic, Heterografts, Humans, Mice, MicroRNAs, original, Proto-Oncogene Proteins c-vav |
| Date Added | 2023/11/20 - 18:08:36 |
| Date Modified | 2023/11/20 - 18:08:56 |
| Notes and Attachments | PubMed entry (Attachment) Texte intégral (Attachment) |
Institut de Recherche en Cancérologie de
