{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T22:59:38Z","timestamp":1792191578681,"version":"4.4.0"},"reference-count":75,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T00:00:00Z","timestamp":1682380800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Toxicol."],"abstract":"<jats:p>The <jats:italic>NF2<\/jats:italic> tumor suppressor gene is a frequent somatically mutated gene in mesothelioma, with 30%\u201340% mesotheliomas showing <jats:italic>NF2<\/jats:italic> inactivation. <jats:italic>NF2<\/jats: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 <jats:italic>NF2<\/jats:italic> alteration may be a late event in mesothelioma development, suggesting that <jats:italic>NF2<\/jats: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 <jats:italic>NF2<\/jats:italic> inactivation in mesothelioma cells remain to be elucidated, targeting the <jats:italic>NF2<\/jats:italic>\/merlin-Hippo pathway may be a new therapeutic strategy for patients with mesothelioma.<\/jats:p>","DOI":"10.3389\/ftox.2023.1161995","type":"journal-article","created":{"date-parts":[[2023,4,25]],"date-time":"2023-04-25T05:14:17Z","timestamp":1682399657000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":37,"title":["NF2 alteration in mesothelioma"],"prefix":"10.3389","volume":"5","author":[{"given":"Yoshitaka","family":"Sekido","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tatsuhiro","family":"Sato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,4,25]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"8090","DOI":"10.1158\/0008-5472.CAN-05-2312","article-title":"A mouse model recapitulating molecular features of human mesothelioma","volume":"65","author":"Altomare","year":"2005","journal-title":"Cancer Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1974","DOI":"10.1016\/s0140-6736(09)60259-2","article-title":"Neurofibromatosis type 2","volume":"373","author":"Asthagiri","year":"2009","journal-title":"Lancet"},{"key":"B3","doi-asserted-by":"publisher","first-page":"e20191257","DOI":"10.1084\/jem.20191257","article-title":"Combined deletion of Bap1, Nf2, and Cdkn2ab causes rapid onset of malignant mesothelioma in mice","volume":"217","author":"Badhai","year":"2020","journal-title":"J. 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