WNT and β-catenin signalling: diseases and therapies

Moon, Randall T.; Kohn, Aimee D.; Ferrari, Giancarlo V. De; Kaykas, Ajamete

doi:10.1038/nrg1427

Cited by 1,678 publications

(1,563 citation statements)

References 106 publications

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“…As increased VEGF-A expression promotes tumoral angiogenesis and subsequent oncogenicity (Ferrara, 2002;Carmeliet, 2003;Ferrara et al, 2003), we analyzed the expression of oncogenic molecules such as Bcl3 and b-catenin, which has been found to be oncogenic when located in the nucleus (Cogswell et al, 2000;Thornburg et al, 2003;Moon et al, 2004;Clevers, 2006). Our results show an important increase in the total amount of both proteins (Figure 1b) and their preferential nuclear localization in the C57-CYLD C/S cells (Figure 3g).…”

Section: Cyld C/s Enhances the Survival Of Malignant Epidermal Cellsmentioning

confidence: 70%

An inactivating CYLD mutation promotes skin tumor progression by conferring enhanced proliferative, survival and angiogenic properties to epidermal cancer cells

et al. 2010

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In this study, we demonstrate that the expression in tumorigenic epidermal cells of a catalytically inactive form of CYLD (CYLD C/S ) that mimics the identified mutations of cyld in human tumors and competes with the endogenous CYLD results in enhanced cell proliferation and inhibition of apoptosis; it also stimulates cell migration and induces the expression of angiogenic factors, including vascular endothelial growth factor-A. Altogether, these characteristics indicate an increased oncogenicity of the tumorigenic epidermal CYLD C/S mutant cells in vitro. Moreover, we show the increase in malignancy of epidermal squamous cell carcinomas that express the CYLD C/S transgene in an in vivo xenograft model. Tumors carrying the mutated CYLD C/S exhibit a fast growth, are poorly differentiated and present a robust angiogenesis. CYLD C/S tumors are also characterized by their elevated proliferation rate and decreased apoptosis. In contrast with previous studies showing the development of benign tumors by mutations in the CYLD gene, here we provide evidence that the occurrence of mutations in the CYLD gene in tumorigenic epidermal cells (carrying previous mutations) increases the aggressiveness of carcinomas, mainly through enhancement of the expression of angiogenic factors, having therefore a key role in epidermal cancer malignancy.

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Section: Cyld C/s Enhances the Survival Of Malignant Epidermal Cellsmentioning

confidence: 70%

An inactivating CYLD mutation promotes skin tumor progression by conferring enhanced proliferative, survival and angiogenic properties to epidermal cancer cells

et al. 2010

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“…Remarkably, it has been reported that Ab neurotoxicity induces the expression of Dickkopf 1 (Dkk1) (Caricasole et al, 2004), which may further antagonize Wnt presentation to its complex receptor. All together the data indicate that the activity of Wnt signaling components is compromised in AD brains and thus underlies Ab generation/toxicity/deposition and tau hyperphosphorylation, major pathological hallmarks of this neurodegenerative condition (De Ferrari and Inestrosa, 2000;Mudher and Lovestone, 2002;Caricasole et al, 2003;Moon et al, 2004).…”

Section: Alzheimer's Disease Apolipoprotein E and Wnt Signalingmentioning

confidence: 96%

The ups and downs of Wnt signaling in prevalent neurological disorders

2006

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In order to function properly, the brain must be wired correctly during critical periods in early development. Mistakes in this process are hypothesized to occur in disorders like autism and schizophrenia. Later in life, signaling pathways are essential in maintaining proper communication between neuronal and non-neuronal cells, and disrupting this balance may result in disorders like Alzheimer's disease. The Wnt/b-catenin pathway has a well-established role in cancer. Here, we review recent evidence showing the involvement of Wnt/b-catenin signaling in neurodevelopment as well as in neurodegenerative diseases. We suggest that the onset/development of such pathological conditions may involve the additive effect of genetic variation within Wnt signaling components and of molecules that modulate the activity of this signaling cascade.

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“…The Wnt pathway plays an important role in cancer (Polakis, 2000;Moon et al, 2004) and thus it is not surprising that Wnt modulators, including Dkks, are also involved.…”

Section: Dkks and Cancermentioning

confidence: 99%

“…Wnts are an evolutionary conserved family of growth factors, whose signaling is involved in numerous processes in development, in the adult and in disease (Cadigan and Nusse, 1997;Moon et al, 2004;Cadigan and Liu, 2006). Wnts are subject to negative and positive regulation by a wide range on effectors that act either intracellularly to modulate components of the signal transduction machinery, or extracellularly to modulate ligand receptor interactions.…”

Section: Introductionmentioning

confidence: 99%