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The Hedgehog (Hh) signaling pathway plays a crucial role in human embryogenesis. It is largely inactive in adult tissues under normal conditions, but evidence of overactive Hh signaling in certain cancers is accumulating. Although this overactivity is caused by mutations in components of the Hh pathway, activation of the pathway in colon, pancreatic, and ovarian tumors is due to overexpression of Hh ligands. In addition, upregulation of Hh signaling has been linked with progression of alcoholic liver disease and with hepatocellular cancer. Given that downregulation of Hh signaling is involved in the early formation of the esophagus, researchers hypothesized that aberrant reactivation of esophageal Hh signaling in adulthood might be linked t…