Intracellular Biomarkers as Regulators of Stemness in Solid Cancers
Both embryonic and CSCs show unlimited growth, invasive capacity and are characterized by an undifferentiated cellular state (481). This feature depends on transitions between epithelial and mesenchymal states, regulated by a network of intracellular pluripotency transcription factors. As reviewed by Hadjimichael et al. and also described by others pluripotency in ESC is regulated by a core-network of transcription factors, consisting amongst others of Oct-3/4, Sox2, Nanog, Klf4, and c-MYC as well as signaling pathways such as the Jak/Stat, Wnt/ß-catenin, Hedgehog/Notch, TGF-ß as well as FGF signaling pathways (367, 482, 483). The core-pluripotency network consisting of Nanog, Oct-3/4 and Sox2 (described in detail below) activates genes of self-renewal and suppresses genes involved in differentiation (482). Pluripotency factors as well as signaling pathways have been indicated as biomarkers for CSCs as shortly described below (compare Tables 1–5). Of note, the tables do not include all biomarkers, however describe the most abundant ones reported in the literature.