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Fig. 4 | Stem Cell Research & Therapy

Fig. 4

From: Characteristics of the cancer stem cell niche and therapeutic strategies

Fig. 4

Key signaling pathways and related targeted inhibitors in the CSC niche. Notch pathway: After twice cleavages by ADAM10/TACE and γ-secretase, respectively, Notch intracellular domain (NICD) is finally released. NICD could translocate into the nucleus and interact with the transcription complex, promoting Notch target gene expression. Wnt pathway: When Wnt proteins bind to the Frizzled family receptors, dishevelled protein (DVL) is activated. DVL would inactivate the multiprotein destruction complex (including APC, Axin, and GSK-3β), which could lead β-catenin to degradation. With the DVL activation, β-catenin starts to accumulate in the cytoplasm. Part of β-catenin enters the nucleus to interact with TCF/LEF and CBP, promoting the expression of target genes. Hedgehog pathway: Binding PTCH with Hh would translocate smoothened (SMO) to the cell membrane and activate it. The activated SMO could easily bind to the COS2/GLI/SUFU complex, then GLI releases from the complex, referred to as GLIa. GLIa activates the transcription of downstream target genes

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