Hedgehog proteins are pivotal morphogens acting through a canonical pathway involving
first activation of ligand binding to Patched followed by alleviation of Smoothened receptor
inhibition, leading to activation of Gli transcription factors. Noncanonical Hedgehog
signaling remains poorly characterized but is thought to be mainly dependent on
Smoothened. However, Smoothened inhibitors have yielded only partial success in
combating Hedgehog signal transduction–dependent cancer, suggesting that noncanonical …