UroToday.com - Tumors share many characteristics with developing embryonic tissues including the presence of rapidly dividing cells and cells in multiple states of differentiation. Therefore, it should not be surprising that the cellular signaling processes that govern normal embryonic development play some role in tumor biology. Hedgehog (Hh) is one of the fundamental developmental signaling pathways that is believed to have a role in prostate cancer. Hh signaling is driven by a family of ligands, referred to as "hedgehogs", that bind to a cell surface receptor protein, Patched, activating a signaling cascade that upregulates gene transcription mediated by Gli transcription factors. For prostate cancer, reports that hedgehog ligands and Gli are overexpressed in the tumor cells supports the idea that these tumor cells might have abnormally activated autocrine Hedgehog signaling. Likewise, experimental evidence that the Hh signaling inhibitor, cyclopamine, or Gli knockdown suppresses prostate cancer cell growth provides pre-clinical evidence to support the use of Hh inhibitors for prostate cancer. However, a recent study from Dr. Wade Bushman's group at the University of Wisconsin1 failed to find any evidence for autocrine hedgehog signaling in the most commonly utilized human prostate cancer cell lines and this report raises important questions regarding the nature of the molecular pathway through which Hh signaling components become dysregulated in prostate cancer…