The spatiotemporal dynamics of epithelial-mesenchymal transition (EMT): Coordinating the tumor microenvironment to promote the metastatic cascade

Epithelial mesenchymal transition (EMT) is a fundamental biological process in tumorigenesis and cancer progression that significantly promotes tumor metastasis and malignant development. Within the tumor microenvironment (TME), various cellular and non-cellular components interact with cancer cells via complex signaling pathways, thereby accelerating the initiation and progression of EMT. Furthermore, EMT and the TME form a positive feedback loop mediated by cytokines, immune cells, metabolic reprogramming, and other factors, which collectively driving tumor metastasis. Targeting this interactive network provides potential strategies to overcome the limitations of current cancer therapies. This review aims to clarify the regulatory effects of various cellular components in the TME on tumor progression and elaborate on the role of TME constituents in promoting EMT. Moreover, the mechanisms underlying the bidirectional regulation between EMT and the TME during cancer metastasis, and are systematically explored. Finally, current therapeutic strategies targeting this network are summarized to provide a theoretical basis for future cancer research and clinical treatment.