Results show that merlin isoform 1 is sufficient to restore normal actin organization in NF2-deficient human tumor cells, demonstrating a key role for merlin in the NF2 phenotype.
Mutations of NF2, the gene for neurofibromatosis 2, are detected in 20-30% of sporadic meningiomas, and almost all mutations lead to loss of merlin expression.
The genetic alterations observed in the NF2 gene indicated that spinal schwannomas are associated with genetic alterations also found in other schwannomas and type 2 Neurofibromatosis, which reinforces the etiological role of this gene.
SPSs express a pattern of biomarkers consistent with the dysregulation of the tumor suppressor merlin observed in neurofibromatosis Type 2-associated schwannomas, suggesting a shared etiology.
In a diverse panel of cancer cell lines, we found that the cells most sensitive to focal adhesion kinase (FAK) inhibition lack expression of the neurofibromatosis type 2 (NF2) tumor suppressor gene product, Merlin.
Last, we found that some NF2 point mutations in merlin most closely resembled gain-of-function alleles in their cellular phenotype, which suggests that mutant NF2 alleles may not always act in a loss-of-function manner, as had been assumed, but may include a spectrum of allelic types with different phenotypic effects on the function of the protein.
Loss of the NF2 tumor suppressor gene is the most common genetic alteration in meningiomas, and the NF2 gene product, Merlin, acts upstream of the Hippo pathway.
Nearly 75% of MM cases have inactivating mutations in the NF2 (neurofibromatosis type 2; Merlin) gene or in downstream signaling molecules of the Hippo signaling cascade, which negatively regulates the transcription factor Yes-associated protein (YAP).
During normal brain development, the neurofibromatosis 2 (NF2) protein suppresses YAP1 activity in neural progenitor cells to promote guidepost cell differentiation, but loss of NF2 causes elevating YAP1 activity in midline neural progenitors, which disrupts guidepost formation.
Inactivation of the NF2 gene leads to neurofibromatosis type-2, which is characterized by multiple benign nervous system tumors and mutations in the gene have been demonstrated in many other tumor types as well.
Neurofibromatosis 2 (NF2) protein (merlin; schwannomin) is a tumor suppressor involved in tumorigenesis of NF2-associated and sporadic schwannomas and meningiomas.
Gene therapy for schwannomas was evaluated in two mouse models of neurofibromatosis type 2 (NF2): (1) a transgenic model in which mice express a dominant mutant form of merlin and spontaneously develop schwannomas, and (2) a xenograft model in which human schwannoma tissue is implanted subcutaneously into immune- compromised mice.
The NF2 gene is a putative tumor-suppressor gene that, when it is altered in the germline, causes neurofibromatosis type 2, a tumor-susceptibility disease that mainly predisposes to schwannomas and meningiomas.
The coexistence of NF2 gene mutations and LOH at the NF2 locus indicates that the NF2 tumor suppressor gene is altered in PNTs by the two-hit mechanism.
Although a great deal of work is ongoing to understand the multiple effects of the lack of the regulating protein Merlin on tumorgenesis in patients with NF2, advances are ongoing with clinical therapeutics.
The NF2-encoded protein Merlin is closely related to the Ezrin-Radixin-Moesin family of membrane/cytoskeleton linker proteins, and has been demonstrated to suppress tumor growth by inhibiting extracellular signal-regulated kinase (ERK) and Rac1 activation.
Finally, we identify several point mutants of Merlin associated with neurofibromatosis type 2 that display an aberrant phosphorylation profile along with defective α-tubulin-binding properties.
This study investigated the correlation between p53 and merlin, a neurofibromatosis 2 (NF2)-related tumor suppressor, in association with the Mdm2 function.
Next-generation sequencing studies and increasingly sophisticated <i>NF2</i>-deletion-based <i>in vitro</i> and <i>in vivo</i> models have helped elucidate the consequences of merlin loss in meningioma pathogenesis.