{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,20]],"date-time":"2026-08-20T15:39:27Z","timestamp":1787240367530,"version":"build-2736575974"},"reference-count":57,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T00:00:00Z","timestamp":1724716800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Ministry of Health &amp; Welfare, Republic of Korea","award":["HR22C1734 and HI14C2296"],"award-info":[{"award-number":["HR22C1734 and HI14C2296"]}]},{"name":"Ministry of Health &amp; Welfare, Republic of Korea","award":["K2023101"],"award-info":[{"award-number":["K2023101"]}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","award":["HR22C1734 and HI14C2296"],"award-info":[{"award-number":["HR22C1734 and HI14C2296"]}],"id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100002642","name":"Korea University","doi-asserted-by":"publisher","award":["K2023101"],"award-info":[{"award-number":["K2023101"]}],"id":[{"id":"10.13039\/501100002642","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Neurofibromatosis type 1 (NF1), an autosomal dominant genetic disorder, is caused by mutations in the NF1 gene, which encodes the GTPase-activating protein neurofibromin. The pathogenesis of the tumor progression of benign plexiform neurofibromas (PNs) and malignant peripheral nerve sheath tumors (MPNSTs) remain unclear. Here, we found that interferon-induced transmembrane protein 1 (IFITM1) was downregulated in MPNST tissues compared to those in PN tissues from patients with NF1. Overexpression of IFITM1 in NF1-associated MPNST cells resulted in a significant decrease in Ras activation (GTP-Ras) and downstream extracellular regulatory kinase 1\/2 (ERK1\/2) phosphorylation, whereas downregulation of IFITM1 via treatment with small interfering RNA in normal Schwann cells had the opposite result, indicating that expression levels of IFITM1 are closely associated with tumor progression in NF1. Treatment of MPNST cells with interferon-gamma (IFN-\u03b3) significantly augmented the expression of IFITM1, thereby leading to a decrease in Ras and ERK1\/2 activation. Despite the small number of patient samples, these findings may potentially provide a new target for chemotherapy in patients with NF1-associated MPNSTs. In xenograft mice injected with MPNST cells, IFN-\u03b3 treatment successfully suppressed tumor progression with increased IFITM1 expression and decreased Ras and ERK1\/2 activation in tumor tissues. Collectively, these results suggest that IFITM1 is closely involved in MPNST pathogenesis and that IFN-\u03b3 is a good candidate for the therapeutic treatment of MPNSTs in NF1.<\/jats:p>","DOI":"10.3390\/ijms25179265","type":"journal-article","created":{"date-parts":[[2024,8,27]],"date-time":"2024-08-27T09:26:51Z","timestamp":1724750811000},"page":"9265","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Interferon-Induced Transmembrane Protein 1 (IFITM1) Is Downregulated in Neurofibromatosis Type 1-Associated Malignant Peripheral Nerve Sheath Tumors"],"prefix":"10.3390","volume":"25","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7860-3459","authenticated-orcid":false,"given":"Gun-Hoo","family":"Park","sequence":"first","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"Jeju Bio Research Center, Jeju Research Institute, Korea Institute of Ocean Science & Technology (KIOST), Jeju-si 63349, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1928-5531","authenticated-orcid":false,"given":"Eunkuk","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"Jeonbuk Institute for Food-Bioindustry, Jeonju 54810, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Su-Jin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kyubin","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jeonghyun","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun Eun","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Pediatrics, Anam Hospital, Korea University College of Medicine, Seoul 02841, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0625-3530","authenticated-orcid":false,"given":"Seon-Yong","family":"Jeong","sequence":"additional","affiliation":[{"name":"Department of Medical Genetics, Ajou University School of Medicine, Suwon 16499, Republic of Korea"},{"name":"Department of Biomedical Sciences, Ajou University Graduate School of Medicine, Suwon 16499, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2024,8,27]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.jaad.2008.12.051","article-title":"Neurofibromatosis type 1","volume":"61","author":"Boyd","year":"2009","journal-title":"J. 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