Metabolic stress and tumor progression : a role for glutamine in fibroblast migration
Tumors are complex tissues composed by multiple cell types, such as cancer associated fibroblasts (CAFs), that facilitate the invasive behavior of tumor cells. When we examined their nutrient requirements, we observed that CAFs rely much more on glutamine than epithelial tumor cells; consequently, t...
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| Tipo de recurso: | tesis doctoral |
| Estado: | Versión publicada |
| Fecha de publicación: | 2020 |
| País: | España |
| Institución: | CBUC, CESCA |
| Repositorio: | TDR. Tesis Doctorales en Red |
| OAI Identifier: | oai:www.tdx.cat:10803/668751 |
| Acceso en línea: | http://hdl.handle.net/10803/668751 |
| Access Level: | acceso abierto |
| Palabra clave: | Glutamine Snail1 Fibroblast activation TGF-β Tumor invasion Glutamina Activació del fibroblast Invasió tumoral 577 |
| Sumario: | Tumors are complex tissues composed by multiple cell types, such as cancer associated fibroblasts (CAFs), that facilitate the invasive behavior of tumor cells. When we examined their nutrient requirements, we observed that CAFs rely much more on glutamine than epithelial tumor cells; consequently, they are more sensitive to glutaminase inhibition. Glutamine-dependence in CAFs promotes their migration and invasion towards this amino acid when challenged with a gradient of glutamine. Moreover, fibroblasts support the collective invasion of epithelial tumor cells towards glutamine, a process that is governed by TGF-β/Snail1-dependent fibroblast activation. Fibroblasts migrating towards glutamine present a polarized distribution of Akt2, that is modulated by the E3 ubiquitin ligase TRAF6 in response to TGF-β stimulation and glutamine availability. In addition, the depletion of this Akt isoform prevents the effect of these cells on epithelial tumor invasion. Therefore, these results demonstrate that the high dependence on glutamine of CAFs promotes nutrient-driven tumor invasion. |
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