Tumor suppressor Nf2/merlin drives Schwann cell changes following electromagnetic field exposure through Hippo-dependent mechanisms.
A ColciagoS MelfiG GiannottiV BonalumeM BallabioL CaffinoF FumagalliValerio MagnaghiPublished in: Cell death discovery (2015)
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.
Keyphrases
- signaling pathway
- induced apoptosis
- pi k akt
- cell cycle arrest
- epithelial mesenchymal transition
- high frequency
- oxidative stress
- cell proliferation
- endoplasmic reticulum stress
- genome wide
- stem cells
- copy number
- peripheral nerve
- cell death
- nuclear factor
- late onset
- immune response
- human health
- single molecule
- high resolution
- protein protein
- toll like receptor
- transcription factor