{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T12:53:17Z","timestamp":1791204797905,"version":"4.1.0"},"reference-count":52,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T00:00:00Z","timestamp":1516233600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T00:00:00Z","timestamp":1516233600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2018,5]]},"abstract":"<jats:p>\n                    Vimentin is a cytoskeletal intermediate filament protein that is expressed in mesenchymal cells and cancer cells during the epithelial\u2010mesenchymal transition. The goal of this study was to identify vimentin\u2010targeting small molecules by using the Tocriscreen library of 1120 biochemically active compounds. We monitored vimentin filament reorganization and bundling in adrenal carcinoma SW13 vimentin\u2010positive (SW13\u2010vim\n                    <jats:sup>+<\/jats:sup>\n                    ) cells\n                    <jats:italic>via<\/jats:italic>\n                    indirect immunofluorescence. The screen identified 18 pharmacologically diverse hits that included 2 statins\u2014simvastatin and mevastatin. Simvastatin induced vimentin reorganization within 15\u201330 min and significant perinuclear bundling within 60 min (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 6.7 nM). Early filament reorganization coincided with increased vimentin solubility. Mevastatin produced similar effects at &gt;1 \u03bcM, whereas the structurally related pravastatin and lovastatin did not affect vimentin.\n                    <jats:italic>In vitro<\/jats:italic>\n                    vimentin filament assembly assays revealed a direct targeting mechanism, as determined biochemically and by electron microscopy. In SW13\u2010vim\n                    <jats:sup>+<\/jats:sup>\n                    cells, simvastatin, but not pravastatin, reduced total cell numbers (IC\n                    <jats:sub>50<\/jats:sub>\n                    = 48.1 nM) and promoted apoptosis after 24 h. In contrast, SW13\u2010vim\n                    <jats:sup>\u2212<\/jats:sup>\n                    cell viability was unaffected by simvastatin, unless vimentin was ectopically expressed. Simvastatin similarly targeted vimentin filaments and induced cell death in MDA\u2010MB\u2010231 (vim\n                    <jats:sup>+<\/jats:sup>\n                    ), but lacked effect in MCF7 (vim\n                    <jats:sup>\u2212<\/jats:sup>\n                    ) breast cancer cells. In conclusion, this study identified vimentin as a direct molecular target that mediates simvastatin\u2010induced cell death in 2 different cancer cell lines.\u2014Trogden, K. P., Battaglia, R. A., Kabiraj, P., Madden, V. J., Herrmann, H., Snider, N. T. An image\u2010based small\u2010molecule screen identifies vimentin as a pharmacologically relevant target of simvastatin in cancer cells. FASEB J. 32, 2841\u20132854 (2018).\n                    <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" xlink:href=\"http:\/\/www.fasebj.org\">www.fasebj.org<\/jats:ext-link>\n                  <\/jats:p>","DOI":"10.1096\/fj.201700663r","type":"journal-article","created":{"date-parts":[[2018,1,18]],"date-time":"2018-01-18T17:38:42Z","timestamp":1516297122000},"page":"2841-2854","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["An image\u2010based small\u2010molecule screen identifies vimentin as a pharmacologically relevant target of simvastatin in cancer cells"],"prefix":"10.1096","volume":"32","author":[{"given":"Kathryn P.","family":"Trogden","sequence":"first","affiliation":[{"name":"Department of Cell Biology and Physiology University of North Carolina\u2013Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Rachel A.","family":"Battaglia","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of North Carolina\u2013Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Parijat","family":"Kabiraj","sequence":"additional","affiliation":[{"name":"Department of Cell Biology and Physiology University of North Carolina\u2013Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victoria J.","family":"Madden","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina\u2013Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harald","family":"Herrmann","sequence":"additional","affiliation":[{"name":"Department of Pathology and Laboratory Medicine University of North Carolina\u2013Chapel Hill Chapel Hill North Carolina USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha T.","family":"Snider","sequence":"additional","affiliation":[{"name":"Institute of Neuropathology University Hospital Erlangen Erlangen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2018,1,18]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1172\/JCI38339"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.105.4.1473"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrc1317"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a018242"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ceb.2014.12.007"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.chembiol.2007.04.010"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bcp.2012.08.027"},{"key":"e_1_2_8_9_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039065"},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2013.284657"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1201735"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/ehv043"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201209028"},{"key":"e_1_2_8_14_1","first-page":"1","article-title":"Isolation of intermediate filament proteins from multiple mouse tissues to study aging\u2010associated post\u2010translational modifications","volume":"123","author":"Battaglia R. 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