Historical Background
Neurofibromatosis type 2 (NF2) is a tumor suppressor gene that when deleted or mutated causes a disorder with the same name. This condition is primarily characterized by benign tumors of the nervous system such as bilateral vestibular schwannomas – originating from Schwann cell – in addition to meningiomas and ependymomas, which arise from cells that make up the membrane surrounding the brain and spinal cord and from the ependyma, a tissue of the central nervous system, respectively (Petrilli and Fernandez-Valle 2016). The incidence ratio of this dominantly inherited disease is 1:25,000, and 50–60% of cases are caused by de novo mutations with somatic mosaicism. NF2somatic mutations have also been found in patients with...
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Ammoun S, Hanemann CO. Emerging therapeutic targets in schwannomas and other merlin-deficient tumors. Nat Rev Neurol. 2011;7(7):392–9.
Bianchi AB, et al. High frequency of inactivating mutations in the neurofibromatosis type 2 gene (NF2) in primary malignant mesotheliomas. Proc Natl Acad Sci U S A. 1995;92(24):10854–8.
Cooper J, Giancotti FG. Molecular insights into NF2/Merlin tumor suppressor function. FEBS Lett. 2014;588(16):2743–52.
Curto M, et al. Contact-dependent inhibition of EGFR signaling by Nf2/Merlin. J Cell Biol. 2007;177(5):893–903.
Horiguchi A, et al. Inactivation of the NF2 tumor suppressor protein merlin in DU145 prostate cancer cells. Prostate. 2008;68(9):975–84.
Houshmandi SS, et al. The neurofibromatosis 2 protein, merlin, regulates glial cell growth in an ErbB2- and Src-dependent manner. Mol Cell Biol. 2009;29(6):1472–86.
James MF, et al. NF2/merlin is a novel negative regulator of mTOR complex 1, and activation of mTORC1 is associated with meningioma and schwannoma growth. Mol Cell Biol. 2009;29(15):4250–61.
Lallemand D, et al. NF2 deficiency promotes tumorigenesis and metastasis by destabilizing adherens junctions. Genes Dev. 2003;17(9):1090–100.
Lau YK, et al. Merlin is a potent inhibitor of glioma growth. Cancer Res. 2008;68(14):5733–42.
Li W, et al. Merlin/NF2 suppresses tumorigenesis by inhibiting the E3 ubiquitin ligase CRL4(DCAF1) in the nucleus. Cell. 2010;140(4):477–90.
Lopez-Lago MA, et al. Loss of the tumor suppressor gene NF2, encoding merlin, constitutively activates integrin-dependent mTORC1 signaling. Mol Cell Biol. 2009;29(15):4235–49.
McClatchey AI, Giovannini M. Membrane organization and tumorigenesis – the NF2 tumor suppressor, Merlin. Genes Dev. 2005;19(19):2265–77.
Morrison H, et al. The NF2 tumor suppressor gene product, merlin, mediates contact inhibition of growth through interactions with CD44. Genes Dev. 2001;15(8):968–80.
Morrow KA, et al. Loss of tumor suppressor Merlin results in aberrant activation of Wnt/beta-catenin signaling in cancer. Oncotarget. 2016;7(14):17991–8005.
Morrow KA, et al. Loss of tumor suppressor Merlin in advanced breast cancer is due to post-translational regulation. J Biol Chem. 2011;286(46):40376–85.
Murray LB, et al. Merlin is a negative regulator of human melanoma growth. PLoS One. 2012;7(8):e43295.
Okada T, et al. Merlin/NF-2 mediates contact inhibition of growth by suppressing recruitment of Rac to the plasma membrane. J Cell Biol. 2005;171(2):361–71.
Petrilli AM, Fernandez-Valle C. Role of Merlin/NF2 inactivation in tumor biology. Oncogene. 2016;35(5):537–48.
Poulikakos PI, et al. Re-expression of the tumor suppressor NF2/merlin inhibits invasiveness in mesothelioma cells and negatively regulates FAK. Oncogene. 2006;25(44):5960–8.
Rong R, et al. Neurofibromatosis 2 (NF2) tumor suppressor merlin inhibits phosphatidylinositol 3-kinase through binding to PIKE-L. Proc Natl Acad Sci U S A. 2004;101(52):18200–5.
Sekido Y, et al. Neurofibromatosis type 2 (NF2) gene is somatically mutated in mesothelioma but not in lung cancer. Cancer Res. 1995;55(6):1227–31.
Shah NR, et al. Analyses of merlin/NF2 connection to FAK inhibitor responsiveness in serous ovarian cancer. Gynecol Oncol. 2014;134(1):104–11.
Shapiro IM, et al. Merlin deficiency predicts FAK inhibitor sensitivity: a synthetic lethal relationship. Sci Transl Med. 2014;6(237):237ra268–8.
Shaw RJ, et al. Regulation of the neurofibromatosis type 2 tumor suppressor protein, merlin, by adhesion and growth arrest stimuli. J Biol Chem. 1998;273(13):7757–64.
Thurneysen C, et al. Functional inactivation of NF2/merlin in human mesothelioma. Lung Cancer. 2009;64(2):140–7.
Zhang N, et al. The Merlin/NF2 tumor suppressor functions through the YAP oncoprotein to regulate tissue homeostasis in mammals. Dev Cell. 2010;19(1):27–38.
Acknowledgments
NIH R01CA138850 and Breast Cancer Research Foundation of Alabama (BCRFA) grants to L.A.S.
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Mota, M., Samant, R.S., Shevde, L.A. (2018). Merlin (NF2). In: Choi, S. (eds) Encyclopedia of Signaling Molecules. Springer, Cham. https://doi.org/10.1007/978-3-319-67199-4_101780
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DOI: https://doi.org/10.1007/978-3-319-67199-4_101780
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