Changes of AXIN-1 and Beta-Catenin in Neuroepithelial Brain Tumors

Martić, Tamara Nikuševa; Pećina‐Šlaus, Nives; Kušec, Vesna; Kokotović, Tomislav; Musinovic, H.; Tomas, Davor; Zeljko, Martina

doi:10.1007/s12253-009-9190-9

Cited by 23 publications

(10 citation statements)

References 21 publications

(25 reference statements)

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“…Our previous study on beta‐catenin expression in neuroepithelial brain tumours of different grades strengthens the claim on Wnt signalling pathway's activity. We have shown that beta‐catenin was upregulated in 53.1% of samples.…”

Section: Discussionsupporting

confidence: 80%

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation

Kafka

Bačić²,

Tomas

et al. 2018

J Cellular Molecular Medi

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Key regulators of the Wnt signalling, DVL1, DVL2 and DVL3, in astrocytomas of different malignancy grades were investigated. Markers for DVL1,DVL2 and DVL3 were used to detect microsatellite instability (MSI) and gross deletions (LOH), while immunohistochemistry and immunoreactivity score were used to determine the signal strengths of the three DVL proteins and transcription factors of the pathway, TCF1 and LEF1. Our findings demonstrated that MSI at all three DVL loci was constantly found across tumour grades with the highest number in grade II (P = 0.008). Collectively, LOHs were more frequent in high‐grade tumours than in low grade ones. LOHs of DVL3 gene were significantly associated with grade IV tumours (P = 0.007). The results on protein expressions indicated that high‐grade tumours expressed less DVL1 protein as compared with low grade ones. A significant negative correlation was established between DVL1 expression and malignancy grades (P < 0.001). The expression of DVL2 protein was found similar across grades, while DVL3 expression significantly increased with malignancy grades (P < 0.001). The signal strengths of expressed DVL1 and DVL3 were negatively correlated (P = 0.002). However, TCF1 and LEF1 were both significantly upregulated and increasing with astrocytoma grades (P = 0.001). A positive correlation was established between DVL3 and both TCF1 (P = 0.020) and LEF1 (P = 0.006) suggesting their joint involvement in malignant progression. Our findings suggest that DVL1 and DVL2 may be involved during early stages of the disease, while DVL3 may have a role in later phases and together with TCF1 and LEF1 promotes the activation of Wnt signalling.

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Section: Discussionsupporting

confidence: 80%

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation

Kafka

Bačić²,

Tomas

et al. 2018

J Cellular Molecular Medi

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“…Our previous study found β-catenin to be upregulated and transferred to the nucleus in astrocytic brain tumors ( 35 ). It was also demonstrated that the transcription factors of the Wnt signaling pathway were upregulated ( 7 ).…”

Section: Discussionmentioning

confidence: 97%

Expression patterns of Wnt signaling component, secreted frizzled-related protein 3 in astrocytoma and glioblastoma

Pećina‐Šlaus

Kafka

Varošanec

et al. 2016

Molecular Medicine Reports

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Secreted frizzled-related protein 3 (SFRP3) is a member of the family of soluble proteins, which modulate the Wnt signaling cascade. Novel research has identified aberrant expression of SFRPs in different types of cancer. In the present study the expression intensities and localizations of the SFRP3 protein across different histopathological grades of astrocytic brain tumors were investigated by immunohistochemistry, digital scanning and image analysis. The results demonstrated that the differences between expression levels and malignancy grades were statistically significant. Tumors were classified into four malignancy grades according to the World Health Organization guidelines. Moderate (P=0.014) and strong (P=0.028) nuclear expression levels were significantly different in pilocytic (grade I) and diffuse (grade II) astrocytomas demonstrating higher expression values, as compared with anaplastic astrocytoma (grade III) and glioblastoma (grade IV). When the sample was divided into two groups, the moderate and high cytoplasmic expression levels were observed to be significantly higher in glioblastomas than in the group comprising astrocytoma II and III. Furthermore, the results indicated that high grade tumors were associated with lower values of moderate (P=0.002) and strong (P=0.018) nuclear expression in comparison to low grade tumors. Analysis of cytoplasmic staining demonstrated that strong cytoplasmic expression was significantly higher in the astrocytoma III and IV group than in the astrocytoma I and II group (P=0.048). Furthermore, lower grade astrocytomas exhibited reduced membranous SFRP3 staining when compared with higher grade astrocytomas and this difference was statistically significant (P=0.036). The present results demonstrated that SFRP3 protein expression levels were decreased in the nucleus in higher grade astrocytoma (indicating the expected behavior of an antagonist of Wnt signaling), whereas when the SFRP3 was located in the cytoplasm an increased expression level of SFRP3 was identified in the high grade astrocytomas when compared with those of a low grade. This may suggest that SFRP3 acts as an agonist of Wnt signaling and promotes invasive behavior.

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“…The three-dimensional structure of the full-length Axin will provide invaluable insights into the details regarding Axin auto-inhibition. On the other hand, increasing evidence indicates a role of Axin in nucleus (Nikuseva Martic et al, 2010; Pecina-Slaus et al, 2011; Schmitz et al, 2013; Willert and Jones, 2006). However, the precise role of nuclear Axin in Wnt signaling remains largely unknown, which warrants further investigation to facilitate our understanding of the function of nuclear Axin as well as its linkage to the cytoplasmic one.…”

Section: Concluding Remarks and Perspectivesmentioning

confidence: 99%

New insights into the regulation of Axin function in canonical Wnt signaling pathway

Song

Wang

2014

Protein Cell

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The Wnt signaling pathway plays crucial roles during embryonic development, whose aberration is implicated in a variety of human cancers. Axin, a key component of canonical Wnt pathway, plays dual roles in modulating Wnt signaling: on one hand, Axin scaffolds the “β-catenin destruction complex” to promote β-catenin degradation and therefore inhibits the Wnt signal transduction; on the other hand, Axin interacts with LRP5/6 and facilitates the recruitment of GSK3 to the plasma membrane to promote LRP5/6 phosphorylation and Wnt signaling. The differential assemblies of Axin with these two distinct complexes have to be tightly controlled for appropriate transduction of the “on” or “off” Wnt signal. So far, there are multiple mechanisms revealed in the regulation of Axin activity, such as post-transcriptional modulation, homo/hetero-polymerization and auto-inhibition. These mechanisms may work cooperatively to modulate the function of Axin, thereby playing an important role in controlling the canonical Wnt signaling. In this review, we will focus on the recent progresses regarding the regulation of Axin function in canonical Wnt signaling.

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Changes of AXIN-1 and Beta-Catenin in Neuroepithelial Brain Tumors

Cited by 23 publications

References 21 publications

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation

Different behaviour of DVL1, DVL2, DVL3 in astrocytoma malignancy grades and their association to TCF1 and LEF1 upregulation

Expression patterns of Wnt signaling component, secreted frizzled-related protein 3 in astrocytoma and glioblastoma

New insights into the regulation of Axin function in canonical Wnt signaling pathway

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