Neurofibromatosis 2 (NF2) is a familial cancer syndrome characterized by the development of multiple brain tumors, including acoustic neuromas (tumors of the otic nerve), meningiomas, and ependymomas (tumors of the linings of the brain). The NF2 gene encodes a tumor suppressor known as Merlin (or NF2), which is mutated in most patients with the disease. Studies in mice with this mutated gene have shown that merlin is involved in regulating cell proliferation. Its loss results in both tumor development and metastasis in mice. The molecular function of merlin is not currently understood, however. Researchers at Massachusetts General Hospital have looked at fibroblasts (connective tissue cells) derived from merlin-deficient mice and compared them to normal mouse fibroblasts. They have shown that while normal cells stop growing when they come into contact with each other, the NF2-deficient cells do not. This suggests that these cells cannot sense when they are touching other cells. Furthermore, the NF2-deficient cells lacked structures called adherens junctions, which connect and are involved in communication between adjacent cells. They have also found that by adding merlin back into the NF2-deficient cells, they could restore the formation of these junctions and subsequently, normal contact-dependent growth inhibition between cells. Therefore, loss of merlin may result in the disruption of normal cellular junctions, cell-to-cell communication and ultimately, contact-dependent growth inhibition leading to tumor growth and metastasis.
Lallemand D, Curto M, Saotome I, Giovannini M, and McClatchey AI. 2003. NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes & Dev. 17:1090-1100.
McClatchey AI, Saotome I, Mercer K, Crowley D, Gusella JF, Bronson RT, Jacks T. 1998. Mice heterozygous for a mutation at the Nf2 tumor suppressor locus develop a range of highly metastatic tumors. Genes Dev. 12:1121-33.
McClatchey AI, Saotome I, Ramesh V, Gusella JF, and Jacks T. 1997. The NF2 tumor suppressor gene product is essential for extraembryonic development immediately prior to gastrulation. Genes & Dev. 11:1253-1265.