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.

MAP17（PDZK1IP1）是一种调节炎症和肿瘤进展的小蛋白，在多种癌症中均被上调。在肿瘤进展期间，MAP17水平在大部分晚期肿瘤中增加。在目前的工作中，我们探索了这种蛋白质塑造肿瘤进化的作用。在这里，我们显示在乳腺癌中，细胞通过脱甲基化通过特定的miRNA下调诱导基因表达的多个变化，从而增加了肿瘤中MAP17的水平。这些miRNA的变化取决于Notch途径的激活。结果，诱导了上皮间质转化（EMT）和干性，从而在体外和体内促进了这些细胞的转移潜力。此外，MAP17会增加肿瘤细胞中的外泌体，其中MAP17被释放为货物，这种水平传播也增加了受体细胞中的EMT。重要的是，培养基中针对MAP17的抗体可减少表达MAP17的细胞中条件培养基促进的EMT和干性改变。因此，MAP17表达通过在肿瘤细胞亚群之间转移MAP17蛋白来促进EMT的水平传播和转移。因此，MAP17可用于描述远距离细胞恶性肿瘤的新机制，而无需涉及遗传或表观遗传修饰。MAP17也可以被视为转移性高度乳腺肿瘤的新靶标。MAP17表达通过在肿瘤细胞亚群之间转移MAP17蛋白来促进EMT的水平传播和转移。因此，MAP17可用于描述远距离细胞恶性肿瘤的新机制，而无需涉及遗传或表观遗传修饰。MAP17也可以被视为转移性高度乳腺肿瘤的新靶标。MAP17表达通过在肿瘤细胞亚群之间转移MAP17蛋白来促进EMT的水平传播和转移。因此，MAP17可用于描述远距离细胞恶性肿瘤的新机制，而无需涉及遗传或表观遗传修饰。MAP17也可以被视为转移性高度乳腺肿瘤的新靶标。