Fig. 1

A schematic representation highlights the role of EMT in tumor metastasis. EMT initiates the metastatic cascade by inducing in situ tumor cells to undergo phenotype transformation. In the intermediate stages of tumor progression, epithelial cells undergo a vital shift in dynamics, losing intercellular adhesions. This triggers their detachment from the primary tumor, allowing subsequent invasive behavior in the nearby microenvironment. Simultaneously, mesenchymal stem cells (MCSCs) undergo a significant metamorphosis, relinquishing connections to play a crucial role in metastasis. Mesenchymal cells, possessing enhanced migratory abilities, orchestrate entry into the circulatory system. They breach the endothelial barrier using active and passive trans-endothelium migration (TEM), engaging intricately with endothelial cells. They infiltrate the mesenchymal stroma, disrupting endothelial junctions and intensifying invasiveness. Circulating tumor cells (CTCs) interact with platelet coagulation factors, producing thrombin, fostering an immune-evasive microenvironment. Neutrophils bind to CTCs, aiding immune evasion and promoting survival. CTCs decelerate, rolling along vessels, eventually halting. MCSCs adhere to the endothelium, transitioning through MET, enabling vascular traversal and colonization