Fig. 4: The role of EMT in the progression and metastasis of CRC.

Colorectal cancer cells undergoing EMT progressively lose intercellular adhesions and acquire the capacity to degrade the basement membrane and ECM. This enables detachment from the primary tumor and invasion into surrounding tissues. EMT-driven cells enhance vascular permeability, facilitating intravasation into the bloodstream. Surviving circulating tumor cells withstand hemodynamic shear forces and resist anoikis before undergoing extravasation at distant sites, initiating metastatic colonization through MET. Within the tumor microenvironment, interactions between cancer cells and stromal components (immune cells, fibroblasts) generate EMT-inducing signals via cytokines and chemokines. Environmental stressors, such as hypoxia, inflammatory signals, and nutrient competition, drive metabolic adaptations like glycolysis, enhancing survival. EMT also confers stemness properties, enabling self-renewal and multi-lineage differentiation potential, ultimately promoting metastatic colonization.