SCs are characterized by their self-renewal capacity and their ability to differentiate into any type of mature cell (Reya et al. 2001; Shakib et al. 2011). Embryonic SCs can differentiate into cells of the three germinal lines to generate all types of tissue (Martin 1981; Evans and Kaufman 1981), while adult SCs are undifferentiated cells that only differentiate into the cell types present in the host tissue, which they can then regenerate (Zhang et al. 2012). The CSC is a recently proposed type of SC that differentiates in an aberrant manner and can produce tumor cell populations that are phenotypically different. According to the CSC hypothesis, CSCs drive tumorige- nesis and tumor growth. However, knowledge of the proportions of CSCs and normal SCs in healthy or tumor tissue is hampered by the lack of specific markers of SCs and CSCs, especially in oral and head and neck squamous cell carcinomas (HNSCCs) (Boman and Wicha 2008). It was recently reported that an HNSCC contains less than one CSC for every 2500 cells (Ishizawa et al. 2010).
Their capacity for self-renewal allows SCs to persist throughout the life of the individual. They must be able to renew and maintain a balance between self-renewal and differentiation, preserving tissue homeostasis (Reya et al. 2001). If cancer is indeed a regulatory disorder of SC self-renewal, it is important to determine the molecular mechanisms that regulate normal SC self-renewal in order to understand the processes underlying tumor cell proliferation.