RT Journal Article
T1 Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells
A1 Garcia-Heredia, Jose Manuel
A1 Otero-Albiol, Daniel
A1 Perez, Marco
A1 Perez-Castejon, Elena
A1 Muñoz-Galvan, Sandra
A1 Carnero, Amancio
K1 Exosomes
K1 MicroRNAs
K1 Carcinoma
K1 Gene expression
K1 Demethylation
K1 Inflammation
K1 Breast neoplasms
K1 MAP17
K1 Neoplasm
K1 Exosomas
K1 MicroARNs
K1 Desmetilación
K1 Inflamación
K1 Neoplasias
K1 Expresión génica
K1 Neoplasias de la mama
AB 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.
PB Springer Nature
YR 2020
FD 2020-10-26
LK http://hdl.handle.net/10668/3871
UL http://hdl.handle.net/10668/3871
LA en
NO García-Heredia JM, Otero-Albiol D, Pérez M, Pérez-Castejón E, Muñoz-Galván S, Carnero A. Breast tumor cells promotes the horizontal propagation of EMT, stemness, and metastasis by transferring the MAP17 protein between subsets of neoplastic cells. Oncogenesis. 2020 Oct 26;9(10):96
DS RISalud
RD Apr 18, 2025