Fig. 3. The plasticity of LCSCs refers to the acquisition of the necessary changes in cell states to facilitate the adaptation of LSCSs to the tumour microenvironment.

This includes plasticity in the form of EMT, metabolic reprogramming and differentiation plasticity. EMT refers to the change from epithelial to mesenchymal states of the cells. Metabolic reprogramming shifts the reliance on glucose and aerobic glycolysis to enhanced mitochondrial respiration and fatty acid oxidation. Differentiation plasticity allows the expansion of hepatic progenitor cells (HPCs) and promotes stemness gene expression. All of these support HCC formation.