Orchestrating the metastatic symphony: the role of extracellular vesicles in the epithelial–mesenchymal transition and pulmonary niche formation of breast cancer

ABSTRACT The complexity of breast cancer (BC) lung metastasis lies in the capacity of tumour cells to interact efficiently with distant organs to promote colonisation, a process that involves the sophisticated coordination of inherent cellular plasticity and the remodelling of the distant microenvironment. This review emphasises the essential function of extracellular vesicles (EVs) within this communication network. Tumour‐derived EVs (TEVs) not only induce epithelial–mesenchymal transition (EMT) by reprogramming breast cancer cell gene expression networks, thereby enhancing migratory and invasive capabilities, but also serve as a ‘vanguard’, arriving in the lungs in advance to educate stromal cells and establish a pre‐metastatic niche that facilitates breast cancer progression. This review uniquely conceptualises EV‐mediated EMT and niche formation as a synergistic and sequential biological continuum. We comprehensively examine the sorting mechanisms of EV molecular cargo, targeted delivery approaches, and hierarchical regulatory networks. Critically, we propose that the concurrent regulation of EMT and niche formation is likely driven by the synergistic action of distinct EV subpopulations rather than single ‘multitasking’ vesicles. Future investigations dissecting this heterogeneity will be pivotal for verifying this synergistic subpopulations hypothesis and establishing a theoretical basis for precise EV‐based metastasis intervention strategies.