Epithelial plasticity and cancer stem cells: Major mechanisms of cancer pathogenesis and therapy resistance

Figure 4 Cancer stem cells, epithelial plasticity and therapeutic strategies. A: Existence of quiescent CSCs that possess the potential to self-renew, ability to proliferate and aberrantly differentiate into heterogeneous lineages of cancer cells and tumor microenvironment by creating immunosuppressive environment regulate epithelial plasticity and enable CSCs to survive, exhibit resistance to growth inhibitory drugs and cause tumor to progress; B: Therapeutic strategies including delivery of miRNA mimics to enforce the expression of tumor suppressor genes, administration of anti-miRNAs to downregulate the expression of oncogenes, shRNA mediated knockdown of oncogenic factors to revert the mesenchymal/CSC phenotype to epithelial non-CSC phenotype and creating inhospitable tumor microenvironment not only confer therapeutic check on epithelial plasticity but also sensitize cancer stem cell populations to the killing effects of therapeutic drugs. CSC: Cancer stem cell; miRNAs: MicroRNAs; ShRNA: Short hairpin RNA.