Activation of Yes-Associated Protein in Low-Grade Meningiomas Is Regulated by Merlin, Cell Density, and Extracellular Matrix Stiffness.

作者: Kuniaki Tanahashi , Atsushi Natsume , Fumiharu Ohka , Kazuya Motomura , Adiljan Alim

DOI: 10.1097/NEN.0000000000000211

关键词: MoesinCell biologyGeneticsMerlin (protein)BiologySubcellular localizationCytoskeletonEzrinRadixinPhosphorylationExtracellular matrix

摘要: The NF2 gene product Merlin is a protein containing ezrin, radixin, and moesin domains; it member of the 4.1 superfamily associated with membrane cytoskeleton also interacts cell surface molecules. mammalian Hippo cascade, downstream signaling cascade merlin, inactivates Yes-associated (YAP). activated by loss functions as an oncogene in meningioma cells; however, factors controlling YAP expression, phosphorylation, subcellular localization meningiomas have not been fully elucidated. Here, we demonstrate that merlin expression heterogeneous 1 gene-negative 3 gene-positive World Health Organization grade I meningiomas. In meningiomas, regions low levels (tumor rims) had greater numbers cells nuclear versus high cores). phosphorylation were affected density IOMM-Lee HKBMM human lines; was regulated extracellular matrix (ECM) stiffness cells. These results suggest ECM may contribute to increased

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