Figure 4.

The diagram shows the process of autophagy and its critical role in regulating the stemness of CSC under various stress conditions, such as hypoxia, nutrient deprivation, increased FAO, elevated ROS, therapeutic interventions, and autophagy activation. Autophagy facilitates the removal of damaged organelles, like mitochondria, protein aggregates, and misfolded proteins and lipids. The degradation products are recycled to provide essential nutrients, which support both CCs and CSCs, preserving their stemness. Inhibition of autophagy at either early or late stages significantly impacts the CSC fate, potentially impairing their stemness and survival. Glycolysis and AMPK signaling also support CSC stemness under stress conditions. These pathways support tumor microenvironment (TME), promoting resilience and therapeutic resistance in CSCs.