Garcia-Heredia, Jose ManuelOtero-Albiol, DanielPerez, MarcoPerez-Castejon, ElenaMuñoz-Galvan, SandraCarnero, Amancio2022-08-032022-08-032020-10-26García-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):96http://hdl.handle.net/10668/3871MAP17 (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.enAtribución 4.0 Internacionalhttp://creativecommons.org/licenses/by/4.0/ExosomesMicroRNAsCarcinomaGene expressionDemethylationInflammationBreast neoplasmsMAP17NeoplasmExosomasMicroARNsDesmetilaciónInflamaciónNeoplasiasExpresión génicaNeoplasias de la mamaMedical Subject Headings::Anatomy::Cells::Cellular Structures::Intracellular Space::Cytoplasm::Cytoplasmic Structures::Organelles::Cytoplasmic Vesicles::Transport Vesicles::ExosomesMedical Subject Headings::Chemicals and Drugs::Nucleic Acids, Nucleotides, and Nucleosides::Antisense Elements (Genetics)::RNA, Antisense::MicroRNAsMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Histologic Type::Neoplasms, Glandular and Epithelial::CarcinomaMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene ExpressionMedical Subject Headings::Diseases::Pathological Conditions, Signs and Symptoms::Pathologic Processes::InflammationMedical Subject Headings::Phenomena and Processes::Genetic Phenomena::Genetic Processes::Gene Expression Regulation::Epigenesis, GeneticMedical Subject Headings::Diseases::NeoplasmsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Diseases::Neoplasms::Neoplastic Processes::Neoplasm MetastasisMedical Subject Headings::Diseases::Neoplasms::Neoplasms by Site::Breast Neoplasmsresearch article33106480open access10.1038/s41389-020-00280-02157-9024PMC7589521