Role of the Hedgehog pathway in hepatocellular carcinoma (review)

The Hedgehog (Hh) pathway is an evolutionarily conserved signaling mechanism that controls many aspects of cell differentiation and the development of tissues and organs during embryogenesis. Early investigations have focused on the effects of Hh activity on the development of organs including skin, gut, the nervous system and bone. However, in addition to normal developmental processes, these investigations also found that Hh signaling is involved in aberrant proliferation and malignant transformation. Consequently, the role of Hh in cancer pathology, and its modulation by environmental factors is the subject of many investigations. Numerous environmental toxins, alcohol, and hepatitis viruses can cause hepatocellular carcinoma (HCC), which is the most common form of liver cancer. Significant hyperactivation of Hh signaling has been observed in liver injury and cirrhosis which often leads to the development of HCC lesions. Moreover, Hh activity plays an important role in the progression of HCC. Here, we review findings relevant to our understanding of the role of Hh signaling in HCC pathogenesis.