In agreement with our hypothesis that HDAC activity is critical for Shh-mediated proliferation, in our studies inhibition of HDAC activity abolished Shh-induced proliferation both in vitro and in vivo. Similarly, the HDAC inhibitor SAHA exhibited anti-tumor activity toward both a xenograft model and transgenice Smo/Smo mice alone or in combination with retinoic acid [28]. Here, SHH is linked to neoplasm.