Prickle-1 Negatively Regulates Wnt/β-Catenin Pathway by Promoting Dishevelled Ubiquitination/Degradation in Liver Cancer

Chan, David W.; Chan, Chung–Yiu; Yam, Judy Wai Ping; Ching, Yick–Pang; Ng, Irene Oi–Lin

doi:10.1053/j.gastro.2006.07.020

Cited by 109 publications

(104 citation statements)

References 32 publications

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“…Its overexpression has been shown to be critical in Wnt/β-catenin signalling activation and β-catenin accumulation in various cancers including HCC [82] . Two inhibitors of Dvl have been identified including Prickle-1 [82] and human homologue of Dapper [83] both of which are reduced in HCC and their reduced expression has significant association with β-catenin accumulation. Peptidyl-prolyl cis/trans isomerase (PIN1) is another positive regulator of the Wnt/β-catenin pathway and functions by inhibiting the interaction between β-catenin and APC [84] .…”

Section: Dvl and Peptidyl-prolyl Cis/trans Isomerasementioning

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%

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Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima¹

2011

WJCO

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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

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Section: Dvl and Peptidyl-prolyl Cis/trans Isomerasementioning

confidence: 99%

Section: Tcf/lefmentioning

confidence: 99%

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Fatima¹

2011

WJCO

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“…The HECT-type ubiquitin ligase NEDL1 ubiquitylates Dvl1 (6), whereas the KLHL12-Cullin-3 ubiquitin ligase targets Dvl3 for degradation (7). Wnt modulators such as Naked cuticle/PR72 and Prickle1 appear to regulate Dvl levels through interaction with ubiquitin ligases (8,9), whereas Dapper 1 seems to target Dvl for lysosomal degradation (10). Inversin, an ankyrin-repeat protein related to the PCP proteins Diversin and Drosophila Dgo, interacts with Dvl and targets cytoplasmic Dvl for ubiquitin-dependent degradation (11).…”

mentioning

confidence: 99%

Regulation of ciliary polarity by the APC/C

Ganner

Lienkamp

Schäfer

et al. 2009

Proc. Natl. Acad. Sci. U.S.A.

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Planar cell polarity signaling controls a variety of polarized cell behaviors. In multiciliated Xenopus epidermal cells, recruitment of Dishevelled (Dvl) to the basal body and its localization to the center of the ciliary rootlet are required to correctly position the motile cilia. We now report that the anaphase-promoting complex (APC/C) recognizes a D-box motif of Dvl and ubiquitylates Dvl on a highly conserved lysine residue. Inhibition of APC/C function by knockdown of the ANAPC2 subunit disrupts the polarity of motile cilia and alters the directionality of the fluid movement along the epidermis of the Xenopus embryo. Our results suggest that the APC/C activity enables cilia to correctly polarize in Xenopus epidermal cells.cilium ͉ Dishevelled ͉ planar cell polarity ͉ polycystic kidney disease ͉ ANAPC2

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“…In contrast, both pk-1 and pk-2 show overlapping expression with components of canonical Wnt signaling, which have been shown to be expressed in the primitive streak (Tcf-1, ␤-catenin and Lef-1), the neural plate (Tcf-3), the dorsomedial epithelial somites and myotome (␤-catenin and Lef-1), and the limb bud mesenchyme (␤-catenin and Tcf-3; Schmidt et al, 2004). It will therefore be interesting to characterize further the importance of vertebrate prickle genes in PCP signaling, as antagonists of canonical Wnt signaling (Veeman et al, 2003;Chan et al, 2006), as well as in other alternative signaling pathways, such as the Notch pathway.…”

Section: Pk-2 Expression In Chicken Embryosmentioning

confidence: 99%

“…Furthermore, while pk function has been well characterized in the context of PCP signals, it is becoming clear that pk homologues have functions beyond establishing PCP. For example, pk-1 antagonizes Wnt/␤-catenin signals in vitro by targeting Dsh for degradation (Veeman et al, 2003;Chan et al, 2006). In addition, recent in vivo studies have identified pk-1 as a regulator of notch activity.…”

Section: Introductionmentioning

confidence: 99%

Expression of avian prickle genes during early development and organogenesis

Cooper

Sweetman

Wagstaff

et al. 2008

Developmental Dynamics

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Chicken homologues of prickle-1 (pk-1) and prickle-2 (pk-2) were isolated to gain insight into the extent of planar cell polarity signaling during avian embryogenesis. Bioinformatics analyses demonstrated homology and showed that pk-1 and pk-2 exhibited conserved synteny with ADAMTS20 and ADAMTS9, GON-related zinc metalloproteases. Expression of pk-1 and pk-2 was established during embryogenesis and early organogenesis, using in situ hybridization and sections of chicken embryos. At early stages, pk-1 was expressed in Hensen's node, primitive streak, ventral neural tube, and foregut. In older embryos, pk-1 transcripts were detected in dorsolateral epithelial somites, dorsomedial lip of dermomyotomes, and differentiating myotomes. Furthermore, pk-1 expression was seen in lateral body folds, limb buds, and ventral metencephalon. pk-2 was expressed in Hensen's node and neural ectoderm at early stages. In older embryos, pk-2 expression was restricted to ventromedial epithelial somites, except in the most recently formed somite pair, and limb bud mesenchyme.

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Prickle-1 Negatively Regulates Wnt/β-Catenin Pathway by Promoting Dishevelled Ubiquitination/Degradation in Liver Cancer

Cited by 109 publications

References 32 publications

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Dickkopfs and Wnt/β-catenin signalling in liver cancer

Regulation of ciliary polarity by the APC/C

Expression of avian prickle genes during early development and organogenesis

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