{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,16]],"date-time":"2026-05-16T22:16:39Z","timestamp":1778969799394,"version":"3.51.4"},"reference-count":59,"publisher":"Wiley","issue":"11","license":[{"start":{"date-parts":[[2012,7,20]],"date-time":"2012-07-20T00:00:00Z","timestamp":1342742400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Glia"],"published-print":{"date-parts":[[2012,11]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Loss of the tumor suppressor merlin causes development of the tumors of the nervous system, such as schwannomas, meningiomas, and ependymomas occurring spontaneously or as part of a hereditary disease Neurofibromatosis Type 2 (NF2). Current therapies, (radio) surgery, are not always effective. Therefore, there is a need for drug treatments for these tumors. Schwannomas are the most frequent of merlin\u2010deficient tumors and are hallmark for NF2. Using our <jats:italic>in vitro<\/jats:italic> human schwannoma model, we demonstrated that merlin\u2010deficiency leads to increased proliferation, cell\u2013matrix adhesion, and survival. Increased proliferation due to strong activation of extracellular\u2010signal\u2010regulated kinase 1\/2 (ERK1\/2) is caused by overexpression\/activation of platelet\u2010derived growth factor receptor\u2010\u03b2 (PDGFR\u2010\u03b2) and ErbB2\/3 which we successfully blocked with AZD6244, sorafenib, or lapatinib. Schwannoma basal proliferation is, however, only partly dependent on PDGFR\u2010\u03b2 and is completely independent of ErbB2\/3. Moreover, the mechanisms underlying pathological cell\u2013matrix adhesion and survival of schwannoma cells are still not fully understood. Here, we demonstrate that insulin\u2010like growth factor\u2010I receptor (IGF\u2010IR) is strongly overexpressed and activated in human primary schwannoma cells. IGF\u2010I and \u2010II are overexpressed and released from schwannoma cells. We show that ERK1\/2 is relevant for IGF\u2010I\u2010mediated increase in proliferation and cell\u2013matrix adhesion, c\u2010Jun N\u2010terminal kinases for increased proliferation and AKT for survival. We demonstrate new mechanisms involved in increased basal proliferation, cell\u2013matrix adhesion, and survival of schwannoma cells. We identified therapeutic targets IGF\u2010IR and downstream PI3K for treatment of schwannoma and other merlin\u2010deficient tumors and show usefulness of small molecule inhibitors in our model. PI3K is relevant for both IGF\u2010IR and previously described PDGFR\u2010\u03b2 signaling in schwannoma. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/glia.22391","type":"journal-article","created":{"date-parts":[[2012,7,21]],"date-time":"2012-07-21T08:53:26Z","timestamp":1342860806000},"page":"1721-1733","source":"Crossref","is-referenced-by-count":23,"title":["The role of insulin\u2010like growth factors signaling in merlin\u2010deficient human schwannomas"],"prefix":"10.1002","volume":"60","author":[{"given":"Sylwia","family":"Ammoun","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. 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