Common dysregulation of Wnt/Frizzled receptor elements in human hepatocellular carcinoma

Bengochea, A.; Souza, M.M. De; Lefrançois, Lydie; Roux, Emilie Le; Galy, Olivier; Chemin, Isabelle; Kim, M M; Wands, Jack R.; Trépo, C.; Hainaut, Pierre; Scoazec, J.Y.; Vitvitski, L.; Merle, Philippe

doi:10.1038/sj.bjc.6604422

Cited by 189 publications

(176 citation statements)

References 39 publications

Supporting

Mentioning

167

Contrasting

Unclassified

Order By: Relevance

“…Furthermore, three other Wnt genes (Wnt3, Wnt4 and Wnt5A), and three FZD genes (FZD3, FZD6 and FZD7) are also upregulated in HCC tissues and preneoplastic peritumoural tissues as compared with normal liver tissues, suggesting that their overexpression may be an early event in hepatocarcinogenesis. However, only the overexpression of FZD7 has been associated with nuclear and/or cytoplasmic accumulation of β-catenin in HCC [70][71][72] .…”

Section: Wnt and Fzdmentioning

confidence: 99%

“…The TCF/LEF family has several spliced forms with unknown functional significance and it is suggested that they may activate preferential genes [86] . In HCC, mutations of TCF-4 are rare with 315 August 10, 2011|Volume 2|Issue 8| WJCO|www.wjgnet.com [70][71][72] phospho-GSK3β High 52 IHC [73] Axin1 Low 67 IHC [76] Dvl High 71 Western blotting [82] Prickle-1 Low 55 PCR [82] HDPR1 Low 58 PCR [83] PIN1 High 53 Western blotting [65] TCF-4 High 91 PCR [87] LEF-1 High 52 IHC [88] CDH17 High 72 IHC [90] CDH17: Cadherin-17; Dvl: Dishevelled; FZD: Frizzled; phospho-GSK3β: Phosphorylated glycogen synthase kinase 3β; HDPR1: Human homologue of Dapper; IHC: Immunohistochemistry; LEF: Lymphoid enhancer factor; PCR: Polymerase chain reaction; PIN1: Peptidyl-prolyl cis/trans isomerase; TCF: T-cell factor.…”

Section: Tcf/lefmentioning

confidence: 99%

See 1 more Smart Citation

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima¹

2011

WJCO

View full text Add to dashboard Cite

Liver cancer is the fifth and seventh most common cause of cancer in men and women, respectively. Wnt/β-catenin signalling has emerged as a critical player in both the development of normal liver as well as an oncogenic driver in hepatocellular carcinoma (HCC). Based on the current understanding, this article summarizes the possible mechanisms for the aberrant activation of this pathway with specific focus on HCC. Furthermore, we will discuss the role of dickkopfs (DKKs) in regulating Wnt/β-catenin signalling, which is poorly understood and understudied. DKKs are a family of secreted proteins that comprise at least four members, namely DKK1-DKK4, which act as inhibitors of Wnt/β-catenin signalling. Nevertheless, not all members antagonize Wnt/β-catenin signalling. Their functional significance in hepatocarcinogenesis remains to be further characterized for which these studies should provide new insights into the regulatory role of DKKs in Wnt/β-catenin signalling in hepatic carcinogenesis. Because of the important oncogenic roles, there are an increasing number of therapeutic molecules targeting β-catenin and the Wnt/ β-catenin pathway for potential therapy of HCC. hepatocellular carcinoma anD the unmet meDical neeDSLiver cancer ranks the fifth most common cancer in men and the second leading cause of cancer-related death. In women, it is the seventh most frequent cancer and sixth leading cause of cancer death [1] . Hepatocellular carcinoma (HCC) is the most common primary malignancy of liver. Men are three times more likely to develop HCC than women and the incidence increases with age [2] . HCC is prevalent in Asia and Africa, but recently it is on the rise in the Western world due to an increase in hepatitis C virus (HCV) infection [3] . Risk factors for HCC include chronic hepatitis B virus (HBV) and HCV infections, cirrhosis, chronic alcohol abuse, aflatoxin ingestion, non-alcoholic steatohepatitis and other metabolic liver diseases [4,5] . Much of HCC occurs in the background of cirrhosis. About 80%-90% of patients with cirrhosis go on to develop HCC eventually and the remaining 10%-20% of cases develop HCC without cirrhosis. Furthermore, HBV and HCV infections increase the risk of developing cirrhosis and later HCC. Among the HCC

show abstract

Section: Wnt and Fzdmentioning

confidence: 99%

Section: Tcf/lefmentioning

confidence: 99%

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima¹

2011

WJCO

View full text Add to dashboard Cite

show abstract

“…First, we focused on Fz3, as it was expressed in HCC cell lines consistently according to a previous report (15). To investigate the role of Fz3 in cell proliferation, we transfected PLC/PRF/5, HLE, Huh-6 and HeLa cells with Fz3-siRNA.…”

Section: Resultsmentioning

confidence: 99%

“…Hepatocellular carcinoma (HCC) arises in liver of Fz7 transgenic mice (13). Fz3, Fz6 and Fz7 genes are upregulated in HCC tissues, compared with surrounding nontumor tissues (14,15). However, because Fz3, Fz6 and Fz7 are expressed in surrounding non-tumor tissues, their clinically mediated inhibition may give rise to adverse effects.…”

Section: Introductionmentioning

confidence: 99%

SiRNA of Frizzled-9 suppresses proliferation and motility of hepatoma cells

Fujimoto

Tomizawa²,

Yokosuka³

2009

Int J Oncol

View full text Add to dashboard Cite

Abstract. Frizzled (Fz), a receptor of Wnt ligands, plays key roles in liver carcinogenesis. Its expression was analyzed as part of a search for a target of molecular therapy for hepatocellular carcinoma (HCC) and hepatoblastoma (HB). Fz genes were analyzed by RT-PCR in HCC cell lines HLE, HLF, PLC/PRF/5, Huh-7 and Hep3B, HB cell lines Huh-6 and HepG2, HeLa cells, human normal fetal and adult liver. We transfected PLC/PRF/5, HLE, Huh-6, and HeLa cells with Fz9-small interfering RNA (Fz9-siRNA). Five days after transfection, cell proliferation was analyzed by MTS assay and cell motility by wound assay with H&E staining. Subsequently, the expressions of cyclin D1 and caspase-3 were analyzed by Western blot analysis. Fz9-siRNA decreased the expression of Fz9 gene in all cell lines. MTS assay showed that Fz9-siRNA significantly suppressed cell proliferation and cell motility in all cell lines. The expression of cyclin D1 was also suppressed by Western blotting. Cleaved caspase-3 did not appear and apoptosis was not observed in any of the cell lines tested. We demonstrated that Fz9 plays an essential role in carcinogenesis of HB and HCC, concluding that Fz9-siRNA could represent a useful therapeutic target for HB and HCC.

show abstract

“…Recent studies have suggested that canonical Wnt signaling pathway is over-activated through FZD7 receptor in many cancers including colorectal, hepatocellular carcinoma (HCC), triple negative breast cancer (TNBC), esophageal cancer, gastric cancer, and Wilm's tumor cell (25)(26)(27)(28)(29)(30).…”

Section: Discussionmentioning

confidence: 99%