Abstract
Relapse of cancer is associated with multidirectional differentiation and unrestricted proliferative replication potential of cancer stem cells. Herein, we propose the plastic differentiation strategy for irreversible differentiation of cancer stem cells; further, salinomycin and its newly constructed functional liposomes are used to implement this strategy. Whole gene, cancer stem cell-related RNA, and protein expression analyses reveal that salinomycin induces the cancer stem cells into normal cells, dormant cells, and mature cancer cells. Besides, the results indicate that the gatekeeper is related to the inhibition of the protein kinase C (PKC) α signaling pathway. The differentiated normal or dormant cells are incorporated into normal tissue, whereas the rest are killed by chemotherapy. The findings would offer the evidence for plastic differentiation of cancer stem cells and propose a novel strategy for cancer therapy.