論文

査読有り
2015年7月

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

JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
  • Kuniaki Tanahashi
  • Atsushi Natsume
  • Fumiharu Ohka
  • Kazuya Motomura
  • Adiljan Alim
  • Ichidai Tanaka
  • Takeshi Senga
  • Ichiro Harada
  • Ryuichi Fukuyama
  • Naoyuki Sumiyoshi
  • Yoshitaka Sekido
  • Toshihiko Wakabayashi
  • 全て表示

74
7
開始ページ
704
終了ページ
709
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1097/NEN.0000000000000211
出版者・発行元
LIPPINCOTT WILLIAMS & WILKINS

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

リンク情報
DOI
https://doi.org/10.1097/NEN.0000000000000211
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/26049897
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000356937000005&DestApp=WOS_CPL
ID情報
  • DOI : 10.1097/NEN.0000000000000211
  • ISSN : 0022-3069
  • PubMed ID : 26049897
  • Web of Science ID : WOS:000356937000005

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