Regulation of self‐renewal in normal and cancer stem cells

Mutations can confer a selective advantage on specific cells, enabling them to go through the multistep process that leads to malignant transformation. The cancer stem cell hypothesis postulates that only a small pool of low‐cycling stem‐like cells is necessary and sufficient to originate and develop the disease. Normal and cancer stem cells share important functional similarities such as ‘self‐renewal’ and differentiation potential. However, normal and cancer stem cells have different biological behaviours, mainly because of a profound deregulation of self‐renewal capability in cancer stem cells. Differences in mode of division, cell‐cycle properties, replicative potential and handling of DNA damage, in addition to the activation/inactivation of cancer‐specific molecular pathways confer on cancer stem cells a malignant phenotype. In the last decade, much effort has been devoted to unravel the complex dynamics underlying cancer stem cell‐specific characteristics. However, further studies are required to identify cancer stem cell‐specific markers and targets that can help to confirm the cancer stem cell hypothesis and develop novel cancer stem cell‐based therapeutic approaches. It has been shown that only a small sub‐population of cells, the cancer stem cells (CSCs), is necessary and sufficient to originate a tumour. We discuss how, compared to normal SCs, CSCs exhibit a profound de‐regulation of their self‐renewal capability, mainly due to differences in mode of division, cell‐cycle properties, replicative potential and handling of DNA‐damage.