Breast cancer: role of Pit-1 and CXCR4/CXCL12 in the metastatic process
The POU1F1 transcription factor (also known Pit-1) is expressed in the mammary gland and its overexpression induces profound phenotypic changes in proteins involved in breast cancer progression. However, some mediators of Pit-1 pro-tumoral actions are still unknown. Here, we show that CXCR4 receptor...
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| Formato: | tesis doctoral |
| Fecha de publicación: | 2019 |
| País: | España |
| Recursos: | Universidad de Santiago de Compostela (USC) |
| Repositorio: | Minerva. Repositorio Institucional de la Universidad de Santiago de Compostela |
| Idioma: | inglés |
| OAI Identifier: | oai:minerva.usc.gal:10347/19865 |
| Acesso em linha: | http://hdl.handle.net/10347/19865 |
| Access Level: | acceso abierto |
| Palavra-chave: | Materias::Investigación::24 Ciencias de la vida::2410 Biología humana::241010 Fisiología humana Materias::Investigación::24 Ciencias de la vida::2411 Fisiología humana::241104 Fisiología endocrina |
| Resumo: | The POU1F1 transcription factor (also known Pit-1) is expressed in the mammary gland and its overexpression induces profound phenotypic changes in proteins involved in breast cancer progression. However, some mediators of Pit-1 pro-tumoral actions are still unknown. Here, we show that CXCR4 receptor and its ligand CXCL12 play a critical role in the pro-tumoral process induced by Pit-1. We found that Pit-1 increases the expression of CXCR4 and CXCL12. Knock-down of CXCR4 reduces tumor growth and spread of Pit-1 overexpressing cells in a zebrafish xenograft model. Furthermore, we described pro-angiogenic effects of Pit-1 through the CXCL12-CXCR4 axis, and that extravasation of Pit-1 overexpressing breast cancer cells is strongly reduced in CXCL12-deprived target tissues. Finally, in breast cancer patients, expression of Pit-1 in primary tumors was found to be positively correlated with CXCR4 and CXCL12, with specific metastasis in liver and lung, and with clinical outcome. Our results suggest that Pit-1-CXCL12-CXCR4 axis could be involved in chemotaxis guidance during the metastatic process, and may represent prognostic and/or therapeutic targets in breast tumors. |
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