<?xml version='1.0' encoding='UTF-8'?><xml><records><record><source-app name="HighWire" version="7.x">Drupal-HighWire</source-app><ref-type name="Journal Article">17</ref-type><contributors><authors><author><style face="normal" font="default" size="100%">Liu, Liming</style></author><author><style face="normal" font="default" size="100%">Zhang, Yichu</style></author><author><style face="normal" font="default" size="100%">Li, Xiaoxue</style></author><author><style face="normal" font="default" size="100%">Mo, Yueni</style></author><author><style face="normal" font="default" size="100%">Song, Lanlan</style></author><author><style face="normal" font="default" size="100%">Jia, Yidi</style></author><author><style face="normal" font="default" size="100%">Zhang, Luoming</style></author><author><style face="normal" font="default" size="100%">Zhou, Wei</style></author><author><style face="normal" font="default" size="100%">Zhang, He</style></author><author><style face="normal" font="default" size="100%">Guo, Hui</style></author><author><style face="normal" font="default" size="100%">Wang, Zhiyong</style></author><author><style face="normal" font="default" size="100%">Cui, Yanfen</style></author><author><style face="normal" font="default" size="100%">Zhang, Fei</style></author><author><style face="normal" font="default" size="100%">Niu, Ruifang</style></author></authors><secondary-authors></secondary-authors></contributors><titles><title><style face="normal" font="default" size="100%">Exosomal EPHA2 transfers metastatic potential by stabilizing TGF-βRI and activating the TGF-β/SMAD3 signaling pathway in breast cancer</style></title><secondary-title><style face="normal" font="default" size="100%">Cancer Biology &amp;amp; Medicine</style></secondary-title></titles><dates><year><style  face="normal" font="default" size="100%">2026</style></year><pub-dates><date><style  face="normal" font="default" size="100%">2026-02-23 00:00:00</style></date></pub-dates></dates><elocation-id><style  face="normal" font="default" size="100%">20250440</style></elocation-id><doi><style  face="normal" font="default" size="100%">10.20892/j.issn.2095-3941.2025.0440</style></doi><volume><style face="normal" font="default" size="100%"></style></volume><issue><style face="normal" font="default" size="100%"></style></issue><abstract><style  face="normal" font="default" size="100%">Objective: Intratumoral heterogeneity refers to the presence of distinct subpopulations of cancer cells within a single tumor, which exhibits variations in phenotypic traits, such as proliferation rate, drug sensitivity, and metastatic potential. Dynamic interactions among heterogeneous cell populations have a critical role in tumor progression. Increasing evidence underscores the importance of intercellular communication among heterogeneous cancer cell subpopulations in driving malignancy. However, the molecular mechanisms governing such cancer cell-to-cancer cell interactions are poorly understood.Methods: Exosomes were isolated from highly metastatic breast cancer cells (HM-BCCs) and low metastatic breast cancer cells (LM-BCCs). The role of exosome-mediated intercellular communication on metastatic behavior was assessed using wound healing and Transwell assays. Gene knockdown and overexpression strategies, small-molecule inhibitors, and xenograft mouse models were used to elucidate the role of exosomal EPHA2.Results: Exosomes derived from HM-BCCs considerably enhanced the migratory and invasive capabilities of LM-BCCs in vitro and increased the metastatic potential in vivo. Mechanistically, EPHA2 was identified as a key protein enriched in exosomes from HM-BCCs and was shown to be transferred to LM-BCCs by these vesicles. Exosomal EPHA2 promoted epithelial-to-mesenchymal transition in LM-BCCs when internalized by stabilizing TGF-βRI and activating the transforming growth factor-β/mothers against decapentaplegic homolog 3 (TGF-β/SMAD3) signaling pathway, thereby facilitating the acquisition of a metastatic phenotype.Conclusions: The results underscore the pivotal function of exosomal EPHA2 in mediating the transfer of metastatic potential among heterogeneous breast cancer cell populations. Targeting the EPHA2-TGF-βRI signaling axis may provide a novel therapeutic approach for preventing or limiting breast cancer metastasis.The data generated in this study are available upon request from the corresponding author.</style></abstract></record></records></xml>