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我们是良性的吗?Wnt信号通路和上皮-间质转化能告诉我们关于颅内脑膜瘤进展的哪些信息?

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

作者信息

Bukovac Anja, Kafka Anja, Raguž Marina, Brlek Petar, Dragičević Katarina, Müller Danko, Pećina-Šlaus Nives

机构信息

Laboratory of Neurooncology, Croatian Institute for Brain Research, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

Department of Biology, School of Medicine, University of Zagreb, 10000 Zagreb, Croatia.

出版信息

Cancers (Basel). 2021 Apr 1;13(7):1633. doi: 10.3390/cancers13071633.

Abstract

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, and , 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 ( = 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 ( = 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.

摘要

上皮-间质转化(EMT)以E-钙黏蛋白表达降低和N-钙黏蛋白表达增加为特征,在肿瘤侵袭和转移中起重要作用。经典Wnt信号通路与EMT密切相关,研究表明β-连环蛋白的核转位可诱导EMT。本研究表明,参与钙黏蛋白转换的基因 和 在脑膜瘤进展中起作用。记录到N-钙黏蛋白相对于E-钙黏蛋白的表达增加。在脑膜瘤中,转录因子SNAIL、SLUG和TWIST1相对于E-钙黏蛋白和N-钙黏蛋白表现出强表达。SNAIL和SLUG的表达与更高分级显著相关(P = 0.001),表明它们在脑膜瘤进展中的作用。更高分级还记录到总β-连环蛋白表达增加,随后其活性形式表达增加(P = 0.000)。本研究给出了参与Wnt和EMT信号通路的重要分子的基因和蛋白质分析结果,揭示了它们在颅内脑膜瘤中的作用。本研究结果为未来研究提供了进展指导和新的标志物,并揭示了治疗干预的新分子靶点。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9ad9/8037732/b2a26a731912/cancers-13-01633-g002.jpg

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