p-1 Integrin is a potential oral SC marker, is expressed in basal keratinocytes and downregulated when cells leave the basal layer (Cotsarelis et al. 1999; Janes et al. 2002). Human keratinocytes can be classified by the rate of their binding with type IV collagen, the natural ligand of p-1 integrin, into two types. Fast-adhering keratinocytes resemble SCs (Jones et al. 1993; Jones 1996), whereas slow-adhering keratinocytes, with low levels of integrin p-1, behave as late ATCs (Jones et al. 1993; Jones 1996), suggesting that integrin p-1 is required to maintain the keratinocytes in an undifferentiated state (Adams and Watt 1989; Levy et al. 2000; Hombach-Klonisch et al. 2008). The main shortcoming of integrin p-1 as a SC marker is its lack of specificity, given that around 20-45% of basal keratinocytes show high integrin p-1 expression.
Transcription Factors Oct3/4, Sox and Nanog
Oct3/4 (Nichols et al. 1998; Niwa et al. 2000), Sox (Avilion et al. 2003) and Nanog (Chambers et al. 2003; Mitsui et al. 2003), play a fundamental role in maintaining the pluripotency and self-renewal of embryonic and adult SCs (Boyer et al. 2005; Loh et al. 2006; Campbell et al. 2007), promoting self-renewal through interaction with Stat-3, Hesx-1, and Zic-3, and signaling molecules TCF-3, FGF-2, and LEFTV2 (Boyer et al. 2005; Loh et al. 2006). Oct3/4 is regarded as one of the best indicators of stemness (de Jong and Looijenga 2006; Marynka-Kalmani et al.
2010). HNSCC cells forming holoclones express high levels of these factors (Lim et al. 2011), suggesting that cancerous cells expressing these factors have SC-like behavior (Zhang et al. 2012).