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Article

Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression

1
Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
2
Department of Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia
3
Department of Neurosurgery, University hospital Dubrava, 10000 Zagreb, Croatia
4
Department of Pathology and Cytology, University Hospital Dubrava, 10000 Zagreb, Croatia
*
Author to whom correspondence should be addressed.
Academic Editors: Sverre Helge Torp and David Scheie
Cancers 2021, 13(7), 1633; https://doi.org/10.3390/cancers13071633
Received: 1 February 2021 / Revised: 17 March 2021 / Accepted: 26 March 2021 / Published: 1 April 2021
(This article belongs to the Special Issue Advances in Research on Human Meningiomas)
Intracranial meningiomas are one of the most common primary brain tumors. Although mostly benign, a small portion may exhibit aggressive and malignant characteristics leading to higher recurrence and mortality rate. Detecting the molecular profiles and genes that are involved in meningioma progression can lead to better stratification of patients and more efficient and targeted treatments. The results of this study reveal the role of main actors of the Wnt signaling pathway (β-catenin) and epithelial to mesenchymal transition (E-cadherin, N-cadherin, TWIST1, SNAIL and SLUG) in progression of these tumors, potentially bringing novel biomarkers in diagnostics and molecular targets for therapeutic interventions.
Epithelial to mesenchymal transition (EMT), which is characterized by the reduced expression of E-cadherin and increased expression of N-cadherin, plays an important role in the tumor invasion and metastasis. Classical Wnt signaling pathway has a tight link with EMT and it has been shown that nuclear translocation of β-catenin can induce EMT. This research has showed that genes that are involved in cadherin switch, CDH1 and CDH2, play a role in meningioma progression. Increased N-cadherin expression in relation to E-cadherin was recorded. In meningioma, transcription factors SNAIL, SLUG, and TWIST1 demonstrated strong expression in relation to E- and N-cadherin. The expression of SNAIL and SLUG was significantly associated with higher grades (p = 0.001), indicating their role in meningioma progression. Higher grades also recorded an increased expression of total β-catenin followed by an increased expression of its active form (p = 0.000). This research brings the results of genetic and protein analyzes of important molecules that are involved in Wnt and EMT signaling pathways and reveals their role in intracranial meningioma. The results of this study offer guidelines and new markers of progression for future research and reveal new molecular targets of therapeutic interventions. View Full-Text
Keywords: epithelial to mesenchymal transition (EMT); Wnt signaling pathway; E-cadherin; N-cadherin; TWIST1; SNAIL and SLUG; β-catenin; intracranial meningioma epithelial to mesenchymal transition (EMT); Wnt signaling pathway; E-cadherin; N-cadherin; TWIST1; SNAIL and SLUG; β-catenin; intracranial meningioma
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MDPI and ACS Style

Bukovac, A.; Kafka, A.; Raguž, M.; Brlek, P.; Dragičević, K.; Müller, D.; Pećina-Šlaus, N. Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression. Cancers 2021, 13, 1633. https://doi.org/10.3390/cancers13071633

AMA Style

Bukovac A, Kafka A, Raguž M, Brlek P, Dragičević K, Müller D, Pećina-Šlaus N. Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression. Cancers. 2021; 13(7):1633. https://doi.org/10.3390/cancers13071633

Chicago/Turabian Style

Bukovac, Anja, Anja Kafka, Marina Raguž, Petar Brlek, Katarina Dragičević, Danko Müller, and Nives Pećina-Šlaus. 2021. "Are We Benign? What Can Wnt Signaling Pathway and Epithelial to Mesenchymal Transition Tell Us about Intracranial Meningioma Progression" Cancers 13, no. 7: 1633. https://doi.org/10.3390/cancers13071633

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