Alterations of Wnt/β-catenin signaling pathway in hepatocellular carcinomas associated with hepatitis C virus

Rogacki, Karol; Kasprzak, Aldona; Stępiński, Adrian

doi:10.5114/pjp.2015.51148

Cited by 21 publications

(16 citation statements)

References 92 publications

(153 reference statements)

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“…Additionally, more studies have proven the tumor-associated role of Wnt signaling in HCV-related HCC[102]. It has been reported that HCV up-regulates microRNA-155 (miR-155), which promotes the nuclear accumulation of CTNNB1 and an accompanying increase in downstream targets[103].…”

Section: Genetic Mechanisms Of Wnt Signaling In Hccmentioning

confidence: 99%

Aberrant regulation of Wnt signaling in hepatocellular carcinoma

Liu

Xie

Chen

et al. 2016

WJG

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Hepatocellular carcinoma (HCC) is one of the most lethal malignancies in the world. Several signaling pathways, including the wingless/int-1 (Wnt) signaling pathway, have been shown to be commonly activated in HCC. The Wnt signaling pathway can be triggered via both catenin β1 (CTNNB1)-dependent (also known as “canonical”) and CTNNB1-independent (often referred to as “non-canonical”) pathways. Specifically, the canonical Wnt pathway is one of those most frequently reported in HCC. Aberrant regulation from three complexes (the cell-surface receptor complex, the cytoplasmic destruction complex and the nuclear CTNNB1/T-cell-specific transcription factor/lymphoid enhancer binding factor transcriptional complex) are all involved in HCC. Although the non-canonical Wnt pathway is rarely reported, two main non-canonical pathways, Wnt/planar cell polarity pathway and Wnt/Ca2+ pathway, participate in the regulation of hepatocarcinogenesis. Interestingly, the canonical Wnt pathway is antagonized by non-canonical Wnt signaling in HCC. Moreover, other signaling cascades have also been demonstrated to regulate the Wnt pathway through crosstalk in HCC pathogenesis. This review provides a perspective on the emerging evidence that the aberrant regulation of Wnt signaling is a critical mechanism for the development of HCC. Furthermore, crosstalk between different signaling pathways might be conducive to the development of novel molecular targets of HCC.

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Section: Genetic Mechanisms Of Wnt Signaling In Hccmentioning

confidence: 99%

Aberrant regulation of Wnt signaling in hepatocellular carcinoma

Liu

Xie

Chen

et al. 2016

WJG

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“…Liu et al [15] reported that in Huh7 cells, HCV core protein enhances Wnt3a-induced β-catenin/Tcf-dependent transcriptional activity via inactivation of glycogen synthase kinase-3β (GSK-3β) activity, thereby promoting the proliferation of Huh7 cells. However, these HCV studies were most often carried out in liver cancer cell lines [16], and only rarely in normal human liver cell lines. Research on the impact of NS4B on the Wnt/β-catenin pathway is also scarce.…”

Section: Introductionmentioning

confidence: 99%

Effects of hepatitis C virus core protein and nonstructural protein 4B on the Wnt/β-catenin pathway

et al. 2017

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BackgroundHepatitis C virus (HCV) core protein and nonstructural protein 4B (NS4B) are potentially oncogenic. Aberrant activation of the Wnt/β-catenin signaling pathway is closely associated with hepatocarcinogenesis. We investigated the effects of HCV type 1b core protein and NS4B on Wnt/β-catenin signaling in various liver cells, and explored the molecular mechanism underlying HCV-related hepatocarcinogenesis.ResultsCompared with the empty vector control, HCV core protein and NS4B demonstrated the following characteristics in the Huh7 cells: significantly enhanced β-catenin/Tcf-dependent transcriptional activity (F = 40.87, P < 0.01); increased nuclear translocation of β-catenin (F = 165.26, P < 0.01); upregulated nuclear β-catenin, cytoplasmic β-catenin, Wnt1, c-myc, and cyclin D1 protein expression (P < 0.01); and promoted proliferation of Huh7 cells (P < 0.01 or P < 0.05). Neither protein enhanced β-catenin/Tcf-dependent transcriptional activity in the LO2 cells (F = 0.65, P > 0.05), but they did significantly enhance Wnt3a-induced β-catenin/Tcf-dependent transcriptional activity (F = 64.25, P < 0.01), and promoted the nuclear translocation of β-catenin (F = 66.54, P < 0.01) and the Wnt3a-induced proliferation of LO2 cells (P < 0.01 or P < 0.05). Moreover, activation of the Wnt/β-catenin signaling pathway was greater with the core protein than with NS4B (P < 0.01 or P < 0.05).ConclusionsHCV core protein and NS4B directly activate the Wnt/β-catenin signaling pathway in Huh7 cells and LO2 cells induced by Wnt3a. These data suggest that HCV core protein and NS4B contribute to HCV-associated hepatocellular carcinogenesis.Electronic supplementary materialThe online version of this article (doi:10.1186/s12866-017-1032-4) contains supplementary material, which is available to authorized users.

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“…The main risk factors for developing HCC are well-known and include cirrhosis, hepatitis B virus (HBV) or hepatitis C virus (HCV) infection, alcohol abuse, aflatoxin B1 ingestion, and non-alcoholic steatohepatitis. Major pathways with frequent mutations in HCC include the telomere maintenance pathway, the cell cycle pathway, the WNT-β-catenin pathway, the epigenetic remodeling pathway, and the chromatin remodeling pathway (3)(4)(5)(6)(7)(8)(9). Despite progress in the diagnosis and treatment of HCC, its prognosis still remains unfavorable.…”

Section: Introductionmentioning

confidence: 99%