Artículo
Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells
Autor/es | García Heredia, José Manuel
Otero Albiol, Daniel Pérez, Marco Pérez Castejón, Elena Muñoz Galván, Sandra Carnero, Amancio |
Departamento | Universidad de Sevilla. Departamento de Bioquímica Vegetal y Biología Molecular |
Fecha de publicación | 2020 |
Fecha de depósito | 2022-03-16 |
Publicado en |
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Resumen | MAP17 (PDZK1IP1) is a small protein regulating inflammation and tumor progression, upregulated in a broad range of carcinomas. MAP17 levels increase during tumor progression in a large percentage of advanced tumors. In the ... MAP17 (PDZK1IP1) is a small protein regulating inflammation and tumor progression, upregulated in a broad range of carcinomas. MAP17 levels increase during tumor progression in a large percentage of advanced tumors. In the present work, we explored the role of this protein shaping tumor evolution. Here we show that in breast cancer, cells increased MAP17 levels in tumors by demethylation induced multiple changes in gene expression through specific miRNAs downregulation. These miRNA changes are dependent on Notch pathway activation. As a consequence, epithelial mesenchymal transition (EMT) and stemness are induced promoting the metastatic potential of these cells both in vitro and in vivo. Furthermore, MAP17 increased the exosomes in tumor cells, where MAP17 was released as cargo, and this horizontal propagation also increased the EMT in the recipient cells. Importantly, an antibody against MAP17 in the media reduces the EMT and stemness alterations promoted by the conditioned media from MAP17-expressing cells. Therefore, MAP17 expression promotes the horizontal propagation of EMT and metastasis by transferring the MAP17 protein between subsets of neoplastic cells. Thus, MAP17 can be used to describe a new mechanism for cell malignity at distance, without the involvement of genetic or epigenetic modifications. MAP17 can also be taken in consideration as new target for metastatic high-grade breast tumors. |
Agencias financiadoras | Ministerio de Ciencia, Innovación y Universidades (MICINN). España Agencia Estatal de Investigación. España European Commission (EC). Fondo Europeo de Desarrollo Regional (FEDER) entro de Investigación Biomédica en Red (CIBER). España Junta de Andalucía |
Identificador del proyecto | RTI2018–097455-B-I00
ROJO2018–102723-T CB16/12/00275 PI-0397–2017 P18-RT-2501 |
Cita | García Heredia, J.M., Otero Albiol, D., Pérez, M., Pérez Castejón, E., Muñoz Galván, S. y Carnero, A. (2020). Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells. Oncogenesis, 9 (10), 96. |
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