AUTHOR=Sekido Yoshitaka , Sato Tatsuhiro 

TITLE=NF2 alteration in mesothelioma

JOURNAL=Frontiers in Toxicology

VOLUME=5

YEAR=2023

URL=https://www.frontiersin.org/journals/toxicology/articles/10.3389/ftox.2023.1161995

DOI=10.3389/ftox.2023.1161995

ISSN=2673-3080

ABSTRACT=<p>The <italic>NF2</italic> tumor suppressor gene is a frequent somatically mutated gene in mesothelioma, with 30%–40% mesotheliomas showing <italic>NF2</italic> inactivation. <italic>NF2</italic> encodes merlin, a member of the ezrin, radixin, and moesin (ERM) family of proteins that regulate cytoskeleton and cell signaling. Recent genome analysis revealed that <italic>NF2</italic> alteration may be a late event in mesothelioma development, suggesting that <italic>NF2</italic> mutation confers a more aggressive phenotype to mesothelioma cells and may not be directly caused by asbestos exposure. The Hippo tumor-suppressive and mTOR prooncogenic signaling pathways are crucial cell-signaling cascades regulated by merlin. Although the exact role and timing of <italic>NF2</italic> inactivation in mesothelioma cells remain to be elucidated, targeting the <italic>NF2</italic>/merlin-Hippo pathway may be a new therapeutic strategy for patients with mesothelioma.</p>