Figure 1.
Cancer stem cell (CSCs) origins and mechanisms of formation. The three hypotheses are highlighted in bold blue arrows. 1. The epithelial to mesenchymal transition (EMT) induced by EMT-inducing factors (EIFs) turns normal epithelial cell (the red square-shaped) to fibroblast-like cell (the blue star-shaped). The latter subsequently becomes CSC particularly with mutations of oncogenes and/or tumor suppressor genes (TSGs). This process mirrors the formation of induced pluripotent cell (iPSC, green round-shaped) from normal fibroblast (red star-shaped) activated by the reprogramming factors (RPFs) shown on the left. 2. Normal adult stem cell (ASC, light-blue round shaped) is transformed into CSC by mutations of oncogene(s) and/or TSG(s). 3. EMT drives the tumor non-CSC (pink pentagon-shaped) back to be CSC.