New roles for Snail1 -expressing CAF during primary tumor progression and secondary niche colonization
Snail1 is the master regulator of the Epithelial-to-Mesenchymal Transition (EMT) and is also crucial for fibroblast activation upon TGFβ signaling. In cancer, Snail1 expression in primary tumors correlates with the appearance of metastasis. We have previously shown that Snail1-expressing cancer-asso...
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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:10803/667308 |
| Acceso en línea: | http://hdl.handle.net/10803/667308 |
| Access Level: | acceso abierto |
| Palabra clave: | Snail1 TGFb Cancer-associated fibroblasts Metastatic colonization Tumor immune evasion Activació del fibroblast Metàstasi Polarització de macròfags Càncer de mama Càncer colorectal 616 |
| Sumario: | Snail1 is the master regulator of the Epithelial-to-Mesenchymal Transition (EMT) and is also crucial for fibroblast activation upon TGFβ signaling. In cancer, Snail1 expression in primary tumors correlates with the appearance of metastasis. We have previously shown that Snail1-expressing cancer-associated fibroblasts (CAF) enhance metastasis. Here we demonstrate that Snail1-expressing CAF attenuate the anti-tumor effector immune response. We observed that Snail1-expressing CAF determine macrophages to present a pro-tumor phenotype in vitro and in the in vivo model of breast cancer MMTV-PyMT what enhanced tumor progression. Moreover, in the context of metastasis, we show that Snail1-dependent TGFβ-induced activation of liver fibroblasts is determinant for colorectal cancer colonization of the organ. Snail1-expressing CAF determine cancer cell evasion of the adaptive anti-tumor effector immunity. In consequence, the absence of Snail1 prevents CAF activation in newly formed metastases and allows immune rejection. These new roles for Snail1-expressing CAF during primary tumor progression and secondary niche colonization increase the relevance of Snail1 protein in oncology. |
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