{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T01:55:38Z","timestamp":1790474138091,"version":"4.1.0"},"reference-count":120,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T00:00:00Z","timestamp":1522022400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"JSPS KAKENHI","award":["15K19015"],"award-info":[{"award-number":["15K19015"]}]},{"name":"JSPS KAKENHI","award":["16H04706"],"award-info":[{"award-number":["16H04706"]}]},{"name":"JSPS KAKENHI","award":["17K19628"],"award-info":[{"award-number":["17K19628"]}]},{"DOI":"10.13039\/100007449","name":"Takeda Science Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100007449","id-type":"DOI","asserted-by":"publisher"}]},{"name":"AMED P-CREATE"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The neurofibromatosis type 2 (NF2) gene encodes merlin, a tumor suppressor protein frequently inactivated in schwannoma, meningioma, and malignant mesothelioma (MM). The sequence of merlin is similar to that of ezrin\/radixin\/moesin (ERM) proteins which crosslink actin with the plasma membrane, suggesting that merlin plays a role in transducing extracellular signals to the actin cytoskeleton. Merlin adopts a distinct closed conformation defined by specific intramolecular interactions and regulates diverse cellular events such as transcription, translation, ubiquitination, and miRNA biosynthesis, many of which are mediated through Hippo and mTOR signaling, which are known to be closely involved in cancer development. MM is a very aggressive tumor associated with asbestos exposure, and genetic alterations in NF2 that abrogate merlin\u2019s functional activity are found in about 40% of MMs, indicating the importance of NF2 inactivation in MM development and progression. In this review, we summarize the current knowledge of molecular events triggered by NF2\/merlin inactivation, which lead to the development of mesothelioma and other cancers, and discuss potential therapeutic targets in merlin-deficient mesotheliomas.<\/jats:p>","DOI":"10.3390\/ijms19040988","type":"journal-article","created":{"date-parts":[[2018,3,26]],"date-time":"2018-03-26T12:08:25Z","timestamp":1522066105000},"page":"988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":106,"title":["NF2\/Merlin Inactivation and Potential Therapeutic Targets in Mesothelioma"],"prefix":"10.3390","volume":"19","author":[{"given":"Tatsuhiro","family":"Sato","sequence":"first","affiliation":[{"name":"Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshitaka","family":"Sekido","sequence":"additional","affiliation":[{"name":"Division of Molecular Oncology, Aichi Cancer Center Research Institute, 1-1 Kanokoden, Chikusa-ku, Nagoya 464-8681, Japan"},{"name":"Department of Cancer Genetics, Nagoya University Graduate School of Medicine, 65, Tsurumai-cho, Showa-ku, Nagoya 464-8603, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2018,3,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"791","DOI":"10.1016\/0092-8674(93)90406-G","article-title":"A novel moesin-, ezrin-, radixin-like gene is a candidate for the neurofibromatosis 2 tumor suppressor","volume":"72","author":"Trofatter","year":"1993","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","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":"ref_3","first-page":"1649","article-title":"Universal absence of merlin, but not other ERM family members, in schwannomas","volume":"151","author":"Xu","year":"1997","journal-title":"Am. 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