Increased β-Catenin/Tcf Signaling in Pilocytic Astrocytomas: A Comparative Study to Distinguish Pilocytic Astrocytomas from Low-Grade Diffuse Astrocytomas

Sareddy, Gangadhara R.; Geeviman, Khamushavalli; Panigrahi, Manas; Challa, Sundaram; Mahadevan, Anita; Babu, Phanithi Prakash

doi:10.1007/s11064-011-0586-z

Cited by 6 publications

(3 citation statements)

References 38 publications

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“…There are several studies investigating the role of Wnt signalling in human astrocytoma . Sareddy et al demonstrated strong expression of TCF4 and LEF1 in diffuse, anaplastic astrocytomas and glioblastomas. They showed that the activation of the transcription factors was induced by β‐catenin migration into the nucleus.…”

Section: Discussionmentioning

confidence: 99%

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: Discussionmentioning

confidence: 99%

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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“…Recent reports of BRAF V600E mutation in malignant peripheral nerve sheath tumors (MPNST), which is one of the distinct types of sarcomas, in conjunction with known BRAF V600E mutations in a subset of GBM , prompted us to investigate whether GS, which is a specific variant of GBM, harbors this particular point mutation. In addition, aberrant Wnt signaling and CTNNB1 (β‐catenin gene) mutations have been described in GBM, but not in GS . Importantly, CTNNB1 mutations are found in soft tissue sarcomas, leading to aberrant β‐catenin nuclear localization .…”

Section: Introductionmentioning

confidence: 99%

Gliosarcomas lack BRAF^V600E mutation, but a subset exhibit β‐catenin nuclear localization

et al. 2016

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Gliosarcoma (GS) is a rare subtype of glioblastoma (GBM) characterized by both glial and mesenchymal components. Unlike GBM, there are no specific prognostic markers, and optimized treatments for patients with GS do not exist. Recent reports describe BRAF mutation in malignant peripheral nerve sheath tumors, and aberrant Wnt signaling and CTNNB1 (β-catenin gene) mutations have been described in GBM. We sought to determine whether GS tumors harbor BRAF mutations or aberrant Wnt signaling, as indicated by nuclear localization of β-catenin, by immunohistochemical detection. Forty-eight (48) cases of primary and secondary adult GS (including recurrent ones) were evaluated by immunohistochemical techniques for the presence of nuclear β-catenin and the BRAF mutation. A small subset (6/46, 13%) showed nuclear localization of β-catenin. None of the cases harbored BRAF mutations (0/48). These results are the first to describe the presence of Wnt signaling pathway abnormalities, manifested by nuclear β-catenin, in a subset, as well as the lack of BRAF mutation in GS. We propose a potential role for Wnt pathway alterations in the pathogenesis of a subset of GS.

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“…Recently, targeting Wnt/β-catenin signaling has attracted considerable attention for glioma therapy. The constitutive activation of Wnt/βcatenin signaling is commonly elevated in malignant gliomas (Gangadhara Reddy, 2012;B. Tang et al, 2012;Wu et al, 2013).…”

mentioning

confidence: 99%

Wnt/β‐catenin signaling cascade: A promising target for glioma therapy

Zhou

Zeng

et al. 2018

Journal Cellular Physiology

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Glioma is one of the most treatment‐refractory intracranial tumors, and the aberrant expressed Wnt/β‐catenin pathway is closely associated with glioma malignancy. In this regard, Wnt/β‐catenin signaling has been reported to play an essential role in cellular proliferation, migration, invasion, and angiogenesis, therefore contributing to glioma progression. However, the underlying mechanisms of Wnt/β‐catenin signaling involvement in gliomagenesis remain unknown. Here, we present an overview of the Wnt components and then go on to summarize the current knowledge describing the multitude of roles of Wnt/β‐catenin in glioma, which are mediated by transcription factors, microRNAs, long noncoding RNAs, and so on. In the latter portion of the review, we elaborate the increasing apparent crosstalk of Wnt/β‐catenin pathway with PI3K/AKT signaling involved in these processes. Ultimately, compounds targeting the Wnt/β‐catenin are described in glioma. As better understanding of the regulatory mechanisms to glioma malignancies increases, Wnt/β‐catenin cascade may represent an area of developmental glioma therapeutics focus.

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Increased β-Catenin/Tcf Signaling in Pilocytic Astrocytomas: A Comparative Study to Distinguish Pilocytic Astrocytomas from Low-Grade Diffuse Astrocytomas

Cited by 6 publications

References 38 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

Gliosarcomas lack BRAF^V600E mutation, but a subset exhibit β‐catenin nuclear localization

Wnt/β‐catenin signaling cascade: A promising target for glioma therapy

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Increased β-Catenin/Tcf Signaling in Pilocytic Astrocytomas: A Comparative Study to Distinguish Pilocytic Astrocytomas from Low-Grade Diffuse Astrocytomas

Cited by 6 publications

References 38 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

Gliosarcomas lack BRAFV600E mutation, but a subset exhibit β‐catenin nuclear localization

Wnt/β‐catenin signaling cascade: A promising target for glioma therapy

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Gliosarcomas lack BRAF^V600E mutation, but a subset exhibit β‐catenin nuclear localization