Molecular mechanisms of Hedgehog signaling in regeneration and malignancy
The Hedgehog signalling pathway has critical roles in embryonic patterning, regeneration, and cancer, yet much remains unknown regarding the molecular mechanisms underlying transmission and reception of the Hedgehog signal. Biochemical and structural studies reveal a surprising role for lipids, with dual modification of the Hedgehog signal by cholesterol and palmitate necessitating specialized proteins like the transporter Dispatched and several lipid-binding carriers for signal export and receptor engagement. Additional lipid transactions mediate signal response, including cholesterol activation of the essential transducer, Smoothened, regulation of Smoothened by the cholesterol transporter and receptor Patched, and blockade of the Patched receptor by the lipid adducts of its ligand, the Hedgehog signal. These signalling events will be discussed alongside of emerging roles for the Hedgehog pathway in control of stem cell proliferation and differentiation, activities critical for maintenance and repair of epithelial organs, but also with profound consequences for the growth and progression of cancers, including urothelial carcinoma.
Professor of Pediatrics and Genetics co-Director of the Cancer Biology PhD program - Elaine and John Chambers - Professor in Pediatric Cancer
Stanford University School of Medicine
Génétique et biologie du développement (UMR3215 / U934)