Snail1 expression in mesenchimal cells promotes tumorigenesis and tumor progression
Snail transcription factor 1 triggers epithelial to mesenchymal transition. In cancer, this process provides tumoral epithelial cells with invasive characteristics. In this thesis, we demonstrated that the function of Snail1 in fibroblasts and mesenchymal stem cells (MSCs) also contributes to tumor...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2016 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/403887 |
| Acceso en línea: | http://hdl.handle.net/10803/403887 |
| Access Level: | acceso abierto |
| Palabra clave: | Snail1 Cancer Fibroblasts activation Invasion Tumorigenesis Cáncer Fibroblastos activos Invasión Tumorigénesis 576 |
| Sumario: | Snail transcription factor 1 triggers epithelial to mesenchymal transition. In cancer, this process provides tumoral epithelial cells with invasive characteristics. In this thesis, we demonstrated that the function of Snail1 in fibroblasts and mesenchymal stem cells (MSCs) also contributes to tumor progression. In tumors with a mesenchymal origin, expression of Snail1 in oncogenic MSCs is needed to maintain their tumorigenic capacity and is required in vivo for tumor formation. Therefore, its deletion results in the absence of tumors. In tumors with an epithelial origin, we demonstrated that Snail1 expression in stromal fibroblasts is required to promote tumor cell invasion. Fibroblasts are activated in a Snail1-dependent manner by factors such as TGF- released by epithelial tumor cells. As response, fibroblasts secrete prostaglandin E2 which contributes to tumor invasion. Consequently, depletion of Snail1 in in vivo cancer models reduces the invasion to adjacent tissues and decreases metastasis. These results suggest a key role for Snail1 in tumor progression that is not limited to its expression in epithelial cells. |
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