Hepatitis B virus X protein stimulates the Hedgehog–Gli activation through protein stabilization and nuclear localization of Gli1 in liver cancer cells

Hedgehog signaling pathway mediates invasion and metastasis of hepatocellular carcinoma via ERK pathway

“…Previous evidence has demonstrated that the Hh signaling plays an important role in multiple tumor types. This signaling pathway is involved in and participates development, invasion and metastasis of HCC [34][35][36][37][38][39][40] . In this study, we further detected expression of Shh and Gli1 in metastasis and non-metastasis HCC liver tissues, simultaneously we used KAAD-cyc, a specific inhibitor of Hh pathway and Shh, a ligand of the Hh pathway in invasion and metastasis assays of human HCC cell line, and we confirmed the results.…”

“…Recent studies have revealed that the Hh signaling pathway is abnormally activated in human HCC [34][35][36] , and this pathway is thought to participate in the development of HCC [37][38][39] . Moreover, activation of the Hh pathway is correlated closely to invasion and metastasis of HCC [36,40] .…”

Hepatitis B and C virus infections as possible risk factor for pancreatic adenocarcinoma

“…In chronic liver diseases, induced by HBV and HCV, virus-related proteins interact with k-Ras, Hedgehog-, Notch-, TGF-band Wnt/b catenin signaling cascades and alter their functions, promoting liver carcinogenesis. Perturbation of these intracellular paths by both viruses has been reported, in vitro, in hepatoma and cancer cell lines [156][157][158][159][160][161]165,166,172,173,[176][177][178][179][180]. Therefore, it may be hypothised that the same viral proteins, which are involved in HCC development, might have analogous activities also in pancreatic cells and favour their malignant transformation.…”

“…-Increased transcription of HypoxiaInducible Factor-1a (HIF-1a) and of its target genes (VEGF and TGF-b), via HCVcore protein [189] Cellular pathways K-Ras-pathway -Interaction with other intracellular signalingcascades, such as Notch pathway; -modulation of different cellular properties (proliferation, differentiation, adhesion and apoptosis) [128][129][130] Increased RAS activity levels beyond a critical threshold caused by: -inflammatory stimuli or spontaneous events; -deletion or mutation of tumor suppressors, including p53, p16 and p19, with deregulation of oncogenecontrolled senescence [130][131][132][133][134] Increased activity, induced by HBx protein, with deregulation of cell-cycle checkpoint controls [160] Increased activity, induced by HCV core and NS5A proteins, with deregulation of cell-cycle checkpoint controls [159] Hedgehog-pathway -Interaction with Wnt/b catenin-, Rasand Transforming growth factor-b pathways; -modulation of different cellular properties (proliferation, differentiation, adhesion and apoptosis) [164][165][166].…”

Mechanisms of HBx Mediated Liver Cancer: Multiple Pathways and Opportunities

“…Given that hedgehog signaling is www.intechopen.com also known to promote tissue remodeling in the liver (Omenetti & Diehl, 2008), it is possible that this may contribute to the progression and formation of cirrhotic nodules in the liver of chronically infected patients. Preliminary data also suggests that HBx activates hedgehog signaling in liver cancer cells (Kim et al, 2011), although the role of this activation in hepatocarcinogenesis remains to be studied. Further, it is not clear whether the upregulation of hedgehog ligands is activated by HBx, and whether this in some way contributes to fibrogenesis.…”