Reappraisal of the Roles of the Sonic Hedgehog Signaling Pathway in Hepatocellular Carcinoma.

Simple Summary: Hepatocellular carcinoma (HCC) remains one of the leading causes of cancer mortality. Treatment of HCC remains challenging, especially for those with advanced stages or those with postoperative recurrence. Molecular research of signaling pathways to afford new options of treatments is urgent. Moreover, among the various signaling pathways, the Sonic hedgehog (SHH) signaling pathway is implicated in multiple aspects of HCC, including cancer development, growth, invasiveness, recurrence, metastasis, the tumor microenvironment, and the maintenance of its cancer stem cells. The SHH signaling pathway also contributes to the resistance of HCC to chemotherapy, target therapy, and radiation therapy. This narrative review of the update studies reappraises the roles of SHH signaling in HCC. A deeper understanding of the SHH signaling pathway is crucial. It may provide more insights into the regulatory processes to establish novel treatments for HCC. HCC remains one of the leading causes of cancer-related death globally. The main challenges in treatments of hepatocellular carcinoma (HCC) primarily arise from high rates of postoperative recurrence and the limited efficacy in treating advanced-stage patients. Various signaling pathways involved in HCC have been reported. Among them, the Sonic hedgehog (SHH) signaling pathway is crucial. The presence of SHH ligands is identified in approximately 60% of HCC tumor tissues, including tumor nests. PTCH-1 and GLI-1 are detected in more than half of HCC tissues, while GLI-2 is found in over 84% of HCC tissues. The SHH signaling pathway (including canonical and non-canonical) is involved in different aspects of HCC, including hepatocarcinogenesis, tumor growth, tumor invasiveness, progression, and migration. The SHH signaling pathway also contributes to recurrence, metastasis, modulation of the cancer microenvironment, and sustaining cancer stem cells. It also affects the resistance of HCC cells to chemotherapy, target therapy, and radiotherapy. Reappraisal of the roles of the SHH signaling pathway in HCC may trigger some novel therapies for HCC. [ABSTRACT FROM AUTHOR]