Hedgehog signaling in human hepatocellular carcinoma

Abstract

Hepatocellular carcinoma (HCC) is the fourth most common malignancy and one of the leading causes of death world wide. Signaling pathways important for tumor initiation and progression in HCC are poorly understood. Hedgehog signaling (Hh) has been implicated in multiple events during development and has also been proposed to play important roles in several tumor types. However, it remains unclear whether this pathway is activated in HCC. We report signaling molecules in the hedgehog pathway that are expressed in both HCC cell lines and tumor samples. Quantitative real-time RT-PCR also reviewed the decreased expression of Hip1 and increased expression of Gli1 and smo in HCC samples compared with non-tumor liver tissues. Blocking the hedgehog pathway with cyclopamine inhibits proliferation, induces apoptosis and repressed Myc-c and cyclin D expression in a subset of HCC cell lines. The study therefore for the first time provides evidence that hedgehog signaling is activated in HCC. The results also indicate that the hedgehog pathway may be a new candidate for therapeutic targeting in HCC.