The cellular story of dishevelleds

Kafka, Anja; Bašić-Kinda, Sandra; Pećina‐Šlaus, Nives

doi:10.3325/cmj.2014.55.459

Cited by 41 publications

(37 citation statements)

References 61 publications

(102 reference statements)

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“…It has long been enigmatic how Wnt signals and Fzd receptors confer pathway specificity (van Amerongen, ). It has, however, become evident that Dvl, an essential component of the destruction complex, is at the heart of the regulation of the specificity (Rothbacher et al, ; Kafka et al, ). In mouse and human, three homologous genes are found: Dvl1, Dvl2, and Dvl3.…”

Section: Wnt Signaling During Heart Developmentmentioning

confidence: 99%

Wnt signaling in the heart fields: Variations on a common theme

Ruiz‐Villalba

Hoppler

Hoff

2016

Developmental Dynamics

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Wnt signaling plays an essential role in development and differentiation. Heart development is initiated with the induction of precardiac mesoderm requiring the tightly and spatially controlled regulation of canonical and noncanonical Wnt signaling pathways. The role of Wnt signaling in subsequent development of the heart fields is to a large extent unclear. We will discuss the role of Wnt signaling in the development of the arterial and venous pole of the heart, highlighting the dual roles of Wnt signaling with respect to its time-and dosage-dependent effects and the balance between the canonical and noncanonical signaling. Canonical signaling appears to be involved in retaining the cardiac precursors in a proliferative and precursor state, whereas noncanonical signaling promotes their differentiation. Thereafter, both canonical and noncanonical signaling regulate specific steps in differentiation of the cardiac compartments. Because heart development is a contiguous, rather than a sequential, process, analyses tend only to show a single timeframe of development. The repetitive alternating and reciprocal effect of canonical and noncanonical signaling is lost when studied in homogenates. Without the simultaneous in vivo visualization of the different Wnt signaling pathways, the mechanism of Wnt signaling in heart development remains elusive. Developmental Dynamics 245:294-306, 2016. V C 2015 Wiley Periodicals, Inc.

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Section: Wnt Signaling During Heart Developmentmentioning

confidence: 99%

Wnt signaling in the heart fields: Variations on a common theme

Ruiz‐Villalba

Hoppler

Hoff

2016

Developmental Dynamics

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“…The components of betacatenin destruction complex represent negative regulators of the pathway. The activation of Wnt signalling pathway also happens in case APC, AXIN and other components of betacatenin destruction complex are mutated and non-functional (MacDonald et al 2009;Polakis 2012;Kafka et al 2014).…”

mentioning

confidence: 99%

Loss of p53 expression is accompanied by upregulation of beta‐catenin in meningiomas: a concomitant reciprocal expression

Pećina‐Šlaus

Kafka

Vladušić

et al. 2016

Int J Experimental Path

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Crosstalk between Wnt and p53 signalling pathways in cancer has long been suggested. Therefore in this study we have investigated the involvement of these pathways in meningiomas by analysing their main effector molecules, beta-catenin and p53. Cellular expression of p53 and beta-catenin proteins and genetic changes in TP53 were analysed by immunohistochemistry, PCR/RFLP and direct sequencing of TP53 exon 4. All the findings were analysed statistically. Our analysis showed that 47.5% of the 59 meningiomas demonstrated loss of expression of p53 protein. Moderate and strong p53 expression in the nuclei was observed in 8.5% and 6.8% of meningiomas respectively. Gross deletion of TP53 gene was observed in one meningioma, but nucleotide alterations were observed in 35.7% of meningiomas. In contrast, beta-catenin, the main Wnt signalling molecule, was upregulated in 71.2%, while strong expression was observed in 28.8% of meningiomas. The concomitant expressions of p53 and beta-catenin were investigated in the same patients. In the analysed meningiomas, the levels of the two proteins were significantly negatively correlated (P = 0.002). This indicates that meningiomas with lost p53 upregulate beta-catenin and activate Wnt signalling. Besides showing the reciprocal relationship between proteins, we also showed that the expression of p53 was significantly (P = 0.021) associated with higher meningioma grades (II and III), while beta-catenin upregulation was not associated with malignancy grades. Additionally, women exhibited significantly higher values of p53 loss when compared to males (P = 0.005). Our findings provide novel information about p53 involvement in meningeal brain tumours and reveal the complex relationship between Wnt and p53 signalling, they suggest an important role for beta-catenin in these tumours.

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“…Therefore, DVLs are considered to be key regulators that rescue cytoplasmic β-catenin from degradation. The overexpression of DVL has been shown to potentiate the activation of Wnt signaling and it is now apparent that upregulation of DVLs is involved in several types of cancer [13,16]. Our present investigations are showing that the dishevelleds, too, are targeted in glioblastoma.…”

mentioning

confidence: 48%

“…In this scenario, TCF/LEF repress target genes through a direct association with corepressors [12]. The activation of Wnt signaling also happens in case APC, AXIN and other components of β-catenin destruction complex are mutated and nonfunctional [9,13].…”

mentioning

confidence: 99%