The <i>NF2</i> gene product, merlin, is a tumor suppressor that is thought to link the actin cytoskeleton with plasma membrane proteins and mediate contact-dependent inhibition of proliferation.
Merlin is thought to play a crucial role as a tumor suppressor not only in hereditary NF2-related tumors, but also in sporadic tumors such as schwannomas, meningiomas and gliomas.
Despite this, somatic or germline mutations in Hippo pathway genes are uncommon, with only the upstream pathway gene neurofibromin 2 (NF2) recognized as a bona fide tumour suppressor gene.
A molecular analysis of single nucleotide polymorphisms (SNPs), which were located in the neurofibromatosis type 2 (NF2) gene, a tumor suppressor gene assigned to chromosome 22q12.3, revealed the loss of heterozygosity (LOH) of the NF2 gene.
Taken together, the results indicated NHERF to be a candidate tumor suppressor gene in human breast carcinoma that may be interconnected to the SYK and MERLIN suppressors.
We hypothesized that the KIT oncogenic form is one of the proteins that modulates expression of the ezrin protein via phosphorylated ezrin at different residues; furthermore, it may interact with the protein merlin, and promoting tumor development via the PI3K or MAPK pathway.
These results suggest that merlin could be a positive regulator of p53 in terms of tumor suppressor activity, and provide the promising therapeutic means for treating tumors with non-functional merlin or Mdm2 overexpression.
GTP binding protein 4(GTPBP4), a member of GTP-binding protein family, was previously characterized as a tumor suppressor that regulates and requires merlin to suppress cell proliferation.
Chromosome 22q carries the locus of a tumor suppressor gene, the neurofibromatosis 2 (NF2) gene, which has been shown to be lost or mutated in some NF2-related tumors, sporadic meningiomas, and vestibular schwannomas, as well as a few other tumors.
Thus, CPI-17 drives Ras activity and tumorigenesis in a two-fold way; inactivation of the tumor suppressor merlin and activation of the growth promoting ERM family.
At least 2 genetic hits (allelic loss and/or gene mutation) in NF2 were found in 16 tumors, seven cases showed 1 hit and 8 tumors showed no NF2 alteration.
Overexpression of NF2 (neurofibromatosis 2, merlin), a tumor suppressor often mutated or lost in MM, did not affect proliferation and viability of CSC-enriched MM populations but robustly decreased the viability of reporter-negative cells.
We demonstrated that tumor-overexpressed 67-kDa laminin receptor (67LR) activates PP2A through adenylate cyclase/cAMP pathway eliciting inhibitions of oncoproteins and activation of tumor suppressor Merlin.
Future research should focus on identifying new therapeutic targets by investigating vestibular schwannoma (epi)genetics, merlin function, and tumor behavior.
However, the absence of mutations in exons 16 and 17 suggests that an inactivating mutation affecting only one of the merlin's alternative termini may not be sufficient to eliminate tumor suppressor function.
However, SMARCB1-associated schwannomas follow a four-hit, three-step model, in which both alleles of SMARCB1 and NF2 genes are inactivated in the tumor, with one of the steps being always the loss of a big part of chromosome 22 involving both loci.
Neurofibromatosis type 2 is an inherited, neoplastic disease associated with schwannomas, meningiomas, and ependymomas and that is caused by inactivation of the tumor suppressor gene <i>NF2</i> The <i>NF2</i> gene product, Merlin, has no intrinsic catalytic activity; its tumor suppressor function is mediated through the proteins with which it interacts.
The lesions stained positively for S-100 protein and a marker antigen for the mutated transgenic NF2 protein, confirming that the imaged tumors and areas of hyperplasia were of Schwann cell origin and expressed the mutated NF2 protein.
Recent progress employing novel mouse targeting strategies has begun to illuminate the roles of the NF1 and NF2 gene products in the molecular pathogenesis of NF-associated tumors.