Deubiquitinating enzymes stabilizing Snail1 transcription factor : a role for USP27X in epithelial-to-mesenchymal transition
Cancer cells undergo epithelial-to-mesenchymal transition (EMT) to dissociate from the primary tumor and to survive to chemotherapy. EMT is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAFs). Snail1 is short-lived in normal epithel...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2019 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/665718 |
| Acceso en línea: | http://hdl.handle.net/10803/665718 |
| Access Level: | acceso abierto |
| Palabra clave: | Epithelial-to-mesenchymal transition (EMT) Sinail1 Deubiquitinase Metastasis Chemo-resistance Transició epiteli-mesènquima Transició epiteli-mesènquima (EMT) Deubiqüitinasa Metàstasi Quimioresistència 576 |
| Sumario: | Cancer cells undergo epithelial-to-mesenchymal transition (EMT) to dissociate from the primary tumor and to survive to chemotherapy. EMT is controlled by Snail1, a transcriptional factor also required for the activation of cancer-associated fibroblasts (CAFs). Snail1 is short-lived in normal epithelial cells as a consequence of the coordinated and continuous ubiquitination by several F-box specific E3 ligases. We have performed a siRNA screening to identify deubiquitinases (enzymes removing the ubiquitin chains conjugated to a substrate), increasing Snail1 stability and identified the Ubiquitin Specific Protease 27X (USP27X) as an enzyme that interacts with, deubiquitinates and stabilizes Snail1. We observed that USP27X modulate EMT features through the stabilization of Snail1, such as tumor cell invasion, cancer metastasis and chemo-resistance. In addition, USP27X is essential for the TGFβ-induced EMT and the activation of CAFs modulated by this cytokine. To summarize, we identified USP27X as a new modulator of Snail1 stabilization and its repression could prevent the metastatic and chemo-resistant proteins of the tumoral cells. |
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