Journal
PATHOLOGY INTERNATIONAL
Volume 61, Issue 6, Pages 331-344Publisher
WILEY
DOI: 10.1111/j.1440-1827.2011.02666.x
Keywords
Hippo signaling cascade; malignant mesothelioma; NF2; oncogene; tumor suppressor gene
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Funding
- Ministry of Education, Culture, Sports, Science and Technology of Japan [H18-1-3-3-1]
- Japan Society for the Promotion of Science [22300338]
- Ministry of Health, Labor and Welfare of Japan
- Takeda Science Foundation
- Grants-in-Aid for Scientific Research [22300338] Funding Source: KAKEN
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Malignant mesothelioma (MM) is an aggressive tumor arising primarily from pleural or peritoneal cavities, which is caused by asbestos exposure after long latency. One of the most frequently mutated genes detected in MM cells is the neurofibromatosis type 2 (NF2) tumor suppressor gene which is located at chromosome 22q12. The NF2 gene encodes Merlin, an ERM (Ezrin/Radixin/Moesin) protein. The underphosphorylated form of Merlin is active and acts as a tumor suppressor by regulating several distinct cellular signaling pathways. One of the downstream pathways regulated by Merlin is the Hippo signaling pathway, which is conserved from Drosophila to mammalian cells and plays important roles in organ size control and cancer development. Recent studies have identified alterations of the components in the Hippo signaling cascade in MM cells, including overexpression of Yes-associated protein (YAP) and inactivation of large tumor suppressor homolog 2 (LATS2). Dysregulation of the Merlin-Hippo signaling cascade is one of the frequent and key events of MM cell development and/or progression. Thus, a strategy to normalize this signaling cascade may be the rationale for developing a new target therapy against MM.
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