Figure 3.

Regulation of self-renewal and DNA-damage response in normal and cancer stem cells. (A) Normal SCs asymmetrically divide, giving rise to stem cells and progenitor cells. Progenitor cells respond to radiation induced damage that induces apoptosis or senescence. SCs lead to the inactivation of apoptotic responses, cell cycle entry and expansion of the SC pool (increasing the rounds of symmetric divisions). Continuous DNA damage and repair suppress apoptosis/senescence, favoring the survival of SCs that harbor DNA mutations. This could have important pathological consequences by generating an actively expanding pool of immortal and genomically unstable SCs, increasing the risk of cancer. (B) In contrast, in cancer stem cells, the self-renewal capability is profoundly deregulated. The CSCs undergo an indefinite number of rounds of cell division, which, ultimately, results in the expansion of the stem cell pool. CSCs are a small but radioresistant cell subpopulation within heterogeneous cancer masses. Under conditions of radiation-induced stress, CSCs survive following IR. However, the majority of non-stem cancer cells are killed via various mechanisms, such as induction of cell apoptosis or mitotic death. A small number of non-stem cancer cells undergo dedifferentiation and transform into CSCs via unknown mechanisms. The newly generated CSCs, together with the intrinsic CSCs, subsequently contribute to the relapse and metastasis of cancer. CSCs, cancer stem cells; IR, irradiation.