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The Hedgehog (Hh) Pathway
Hh signaling pathway is essential in mammalian
embryonic development and adult tissue
homeostasis
1
Mechanism:
2,3
•
PTCH inhibits SMO
•
Hh ligand binding to PTCH relieves inhibition of
SMO
•
SMO signaling, via SUFU, activates GLI
transcription factors
Constitutive activation can result from mutations
(
PTCH
,
SMO
or
SUFU
) or overexpression of the
ligands
4–8
•
Hypermethylation of
PTCH
and the negative
regulator HIP1 can lead to pathway activation
9,10
COS, conserved ortholog set; GLI, glioma-associated oncogene; Hh, hedgehog; HIP1, hedgehog interating protein 1; PTCH, patched; SMO, smoothened;
SUFU, suppressor of fused
1. Jiang J, Hui C. Dev Cell 2008; 2. Epstein EH. Nat Rev Cancer 2008; 3. Xie J. Acta Biochim Biophys Sin (Shanghai) 2008; 4. Slade I , et al. Fam Cancer
2011; 5. Lee Y , et al. Cancer Res 2003; 6. Scott DK , et al. Cell Cycle 2006; 7. Zurawel RH, et al. Genes Chromosomes Cancer 2000; 8. Thompson MC, et
al. JCO 2006; 9. Shahi MH, et al. BMC Cancer 2010; 10. Shahi MH, et al. J Neurooncol 2011.
SMO
Target
Genes