Abstract
Previous evidence showed mutations of the neurofibromin type 2 gene (Nf2), encoding the tumor suppressor protein merlin, in sporadic and vestibular schwannomas affecting Schwann cells (SCs). Accordingly, efforts have been addressed to identify possible factors, even environmental, that may regulate neurofibromas growth. In this context, we investigated the exposure of SC to an electromagnetic field (EMF), which is an environmental issue modulating biological processes. Here, we show that SC exposed to 50 Hz EMFs changes their morphology, proliferation, migration and myelinating capability. In these cells, merlin is downregulated, leading to activation of two intracellular signaling pathways, ERK/AKT and Hippo. Interestingly, SC changes their phenotype toward a proliferative/migrating state, which in principle may be pathologically relevant for schwannoma development.
Highlights
Neurofibromin 2 gene (Nf2) encodes the tumor suppressor protein merlin, a cytoskeleton-associated protein belonging to the ERM family
The aim of the present study was to investigate whether the tumor suppressor merlin may regulate cellular and biochemical features, such as morphology, viability, proliferation, and myelinating capability of Schwann cells (SCs) exposed to electromagnetic field (EMF)
EMF exposure induced morphologic rearrangements in actin cytoskeleton, which might be critical for SCs differentiation and myelination
Summary
Neurofibromin 2 gene (Nf2) encodes the tumor suppressor protein merlin, a cytoskeleton-associated protein belonging to the ERM (ezrin-radixin-moesin) family. Mutations in the Nf2 gene origin an autosomal dominant multiple syndrome called neurofibromatosis type 2,1 leading to merlin loss and determining the transformation of Schwann cells (SCs) into a form of benign tumor called schwannoma. About 5% of vestibular schwannomas (which are neurofibromas originating from the SC of the eighth cranial vestibular nerve) are related to inherited Nf2 mutations, whereas the remaining 95% are sporadic.[2] between 30 and 50% of new cases arise by random genetic mutations.[3] merlin is mutated at least in 66% of sporadic schwannomas indicating a correlation between this protein and tumor development.[4]. Recent research on Nf2 gene showed that merlin is involved in different signal transduction pathways, including MAPK/ERK and Hippo pathways.[5,6] in merlin null schwannomas the MAPK/ERK pathway is activated,[6] whereas the Hippo pathway is involved in several cell transformations,[7] mostly through control of the transcriptional co-activator Yes-associated protein (Yap).[8]
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