Genetic alterations of
neurofibromatosis type 2 (NF2) gene lead to the development of
schwannomas,
meningiomas, and
ependymomas. Mutations of NF2 gene were also found in
thyroid cancer,
mesothelioma, and
melanoma, suggesting that it functions as a
tumor suppressor in a wide spectrum of cells. The product of NF2 gene is
merlin (
moesin-ezrin-radixin-like protein), a member of the Band 4.1 superfamily
proteins.
Merlin shares significant sequence homology with the ERM (
Ezrin-
Radixin-
Moesin) family
proteins and serves as a linker between transmembrane
proteins and the actin-cytoskeleton.
Merlin is a multifunctional
protein and involved in integrating and regulating the extracellular cues and intracellular signaling pathways that control cell fate, shape, proliferation, survival, and motility. Recent studies showed that
merlin regulates the cell-cell and cell-matrix adhesions and functions of the cell surface adhesion/
extracellular matrix receptors including CD44 and that
merlin and CD44 antagonize each other's function and work upstream of the mammalian Hippo signaling pathway. Furthermore,
merlin plays important roles in stabilizing the contact inhibition of proliferation and in regulating activities of several
receptor tyrosine kinases. Accumulating data also suggested an emerging role of
merlin as a negative regulator of growth and progression of several non-NF2 associated
cancer types. Together, these recent advances have improved our basic understanding about
merlin function, its regulation, and the major signaling pathways regulated by
merlin and provided the foundation for future translation of these findings into the clinic for patients bearing the
cancers in which
merlin function and/or its downstream signaling pathways are impaired or altered.