Fig. 3

The signaling pathways controlling CSCs. Several signaling pathways play critical roles in malignancy transformation and tumor development, particularly within the CSC regulatory network. The accompanying figure introduces the five primary signaling pathways and outlines the mechanisms of signal transmission within each pathway. Notably, in the Notch signaling pathway, the core component, NICD, undergoes three cleavage events before entering the nucleus to promote gene transcription. Shh signaling can be activated in CSCs by inhibiting SMO-mediated Gli cleavage. WNT/β-catenin signaling is facilitated by the accumulation of inactive β-catenin, regulated by GSK-3β, and requires the involvement of Axin and Dishevelled. TGF-β recruits its receptors and initiates phosphorylation through serine/threonine kinase domains, subsequently translocating phosphorylated SMAD into the nucleus. In the JAK/STAT3 signaling pathway, signals are transmitted through transphosphorylation events downstream