Sekido Yoshitaka, Sato Tatsuhiro
Division of Cancer Biology, Aichi Cancer Center Research Institute, Nagoya, Japan.
Division of Molecular and Cellular Oncology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Front Toxicol. 2023 Apr 25;5:1161995. doi: 10.3389/ftox.2023.1161995. eCollection 2023.
The tumor suppressor gene is a frequent somatically mutated gene in mesothelioma, with 30%-40% mesotheliomas showing inactivation. 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 alteration may be a late event in mesothelioma development, suggesting that 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 inactivation in mesothelioma cells remain to be elucidated, targeting the /merlin-Hippo pathway may be a new therapeutic strategy for patients with mesothelioma.
肿瘤抑制基因是间皮瘤中常见的体细胞突变基因，30%-40%的间皮瘤显示该基因失活。它编码merlin，merlin是埃兹蛋白、根蛋白和膜突蛋白（ERM）家族的成员，该家族蛋白调节细胞骨架和细胞信号传导。最近的基因组分析表明，该基因改变可能是间皮瘤发生过程中的晚期事件，这表明该基因突变赋予间皮瘤细胞更具侵袭性的表型，且可能并非直接由石棉暴露引起。Hippo肿瘤抑制信号通路和mTOR促癌信号通路是由merlin调节的关键细胞信号级联反应。尽管该基因在间皮瘤细胞中失活的确切作用和时间仍有待阐明，但靶向该基因/merlin-Hippo信号通路可能是间皮瘤患者的一种新治疗策略。
