Fig. 5: Alterations in energy metabolism during the biological processes of tumor cells.

Proliferating cells exhibit a preference glycolysis rather than OXPHOS, whereas quiescent cells demonstrate reduced reliance on glycolysis and increased dependence on OXPHOS. The metabolic flexibility during tumor metastasis confers a survival advantage, as cancer cells undergo numerous dynamic changes and metabolic adaptations. The process of EMT is closely associated with upregulated glycolysis or heightened levels of both glycolysis and OXPHOS activity. While traveling to distant organs, CTCs utilize OXPHOS as their primary energy source. The formation of clusters among CTCs is correlated with their ability to colonize distant metastatic sites, as these clusters exhibit enhanced glycolysis and decreased dependence on OXPHOS. The induction of MET significantly increases OXPHOS levels beyond those observed pre-EMT, solely restoring the glycolytic rate in cancer cells to its pre-EMT state. The metabolic dependencies of tumor cells at metastatic sites rely on the synchronized metabolic pathways between cancer cells and the secondary site microenvironment. Some metastatic tumor cells rely on OXPHOS, while others depend on glycolysis.