| Autor: |
Bukovac, Anja, Kafka, Anja, Blažević, Božana, Katić, Matea, Marjanović, Lovro, Dragičević, Katarina, Jakovčević, Antonia, Mϋller, Danko, Marčić, Kristijan, Pećina-Šlaus, Nives |
| Jazyk: |
angličtina |
| Rok vydání: |
2022 |
| Předmět: |
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| Popis: |
Meningioma progression and invasion is usually attributed to higher tumor grades (II and III) which are less likely to be found in the population but are more difficult to treat. However, new findings suggest that grade I or benign meningioma can also harbor invasive molecular characteristics. Epithelial to mesenchymal transition (EMT) is a leading process governing tumor invasion that has also been implicated in progression of intracranial meningioma. The most prominent feature of EMT is a cadherin switch responsible for the loss of cellular epithelial properties (loss of E- cadherin) and gain of mesenchymal ones (gain of N- cadherin). We studied this feature in meningiomas of different grades along with EMT transcriptional activity and the activation of closely related Wnt signaling pathway. The results of our analysis showed that CDH2 (N-cadherin) was very frequently mutated with 70% of samples harboring MSI and/or loss of heterozygosity while CDH1 (E-cadherin) was lost in 12.5% of samples. Furthermore, microsatellite instability (MSI) was the major genetic aberration in both E- and N-cadherin, found in 19, 4% and 40% of samples, respectively. Investigation on protein levels showed that N- cadherin expression was a bit higher than E- cadherin which was lost in 30% of samples. The presence of both proteins suggests partial EMT, which is considered more effective for invasion than when E-cadherin is completely lost. The immunohistochemistry results revealed strong expression of EMT transcription factors: TWIST1, SNAIL and SLUG, where SNAIL and SLUG expression was significantly correlated to higher grades (p=0, 001). Key regulators of Wnt signaling – β- catenin and DVL1, were also activated and associated with meningioma progression. The higher nuclear expression of DVL1 was significantly associated with higher meningioma grades (p=0.030) and accompanied with higher levels of active β- catenin (p=0.029). Mutational hotspot of CTNNB1 (β-catenin) exon 3 was sequenced showing 22, 2% of samples with mutations, which may result in faulty protein product as predicted by Porter 5.0: Prediction of protein secondary structure. Our results showed cadherin switch and strong EMT transcriptional activity, as well as the activation of Wnt signaling pathway, which can all contribute to meningioma progression. |
| Databáze: |
OpenAIRE |
| Externí odkaz: |
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