Figure 2

Signaling pathways in PCSCs. The HH and Notch developmental pathways are highly active in PCSCs and may be activated by a series of respective ligands. The SHH/Gli signaling pathway plays a pivotal role in maintenance of stemness (self-renewal) via regulation of the expression of the pluripotency-maintaining factors Nanog, Oct4, c-Myc, and Sox2. Upon activation by interaction with ligands, Notch is cleaved and translocated to the nucleus for transcriptional activation of Notch target genes, including hairy and enhancer of split-1, nuclear factor κB (NF-κB), cyclin D1, and c-Myc. The Wnt/β-catenin pathway is vitally involved in cell fate determination via binding to the transcription factor T-cell factor/lymphocyte enhancer factor (TCF/LEF). PI3K/AKT signaling is involved in PCSCs by directly interacting with CD133. FOXM1 plays a pivotal role in PCSCs by directly stimulating stem-like characteristics and cross-talk with other pathways. Abnormal signaling pathways also may involve PCSCs but are not illustrated in this figure. IGF, insulin-like growth factor; EGF, epidermal growth factor; Jag, Jagged; IGF-1R, insulin-like growth factor-1 receptor; EGFR, epidermal growth factor receptor; ICN, intracellular domain of Notch.