Colon cancer stemness as a reversible epigenetic state: Implications for anticancer therapies

Figure 1 The cancer cell plasticity model reconciles cancer stem cell and stochastic models. A: In the stochastic model, cancer cells are heterogeneous because of accumulation of genetic and epigenetic alterations acquired through excessive proliferation, but most cells are able to proliferate and initiate new tumors; B: In the cancer stem cell model, cancer cells are organized in a hierarchy comparable to normal tissues where CSCs (in purple) are the only cells able to regenerate a tumor with its whole heterogeneity; C: In the cancer plasticity model, cancer cells are able to rapidly switch back and forth between a stem and a non-stem state. CSCs change to non-stem cell most likely occurs through epigenetic programming and silencing of cancer stem cell/pluripotency markers. Reprogramming, leading to induced CSCs (in green) from non-stem cancer cells, can either occur through reversible epigenetic modifications or genetic alterations, hence leading to a new clonal population of cancer cells in the tumor. CSC: Cancer stem cell; iCSC: Induced CSC.