{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T14:28:04Z","timestamp":1781101684654,"version":"3.54.1"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"7","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2001,3,27]]},"abstract":"<jats:p>\n                    Lethal factor is a protease, one component of\n                    <jats:italic>Bacillus\n anthracis<\/jats:italic>\n                    exotoxin, which cleaves many of the mitogen-activated\n protein kinase kinases (MEKs). Given the importance of MEK signaling in\n tumorigenesis, we assessed the effects of anthrax lethal toxin (LeTx)\n on tumor cells. LeTx was very effective in inhibiting mitogen-activated\n protein kinase activation in V12 H-ras-transformed NIH 3T3 cells.\n                    <jats:italic>In vitro<\/jats:italic>\n                    , treatment of transformed cells with LeTx\n caused them to revert to a nontransformed morphology, and inhibited\n their abilities to form colonies in soft agar and to invade Matrigel\n without markedly affecting cell proliferation.\n                    <jats:italic>In vivo<\/jats:italic>\n                    ,\n LeTx inhibited growth of ras-transformed cells implanted in athymic\n nude mice (in some cases causing tumor regression) at concentrations\n that caused no apparent animal toxicity. Unexpectedly, LeTx also\n greatly decreased tumor neovascularization. These results demonstrate\n that LeTx potently inhibits ras-mediated tumor growth and is a\n potential antitumor therapeutic.\n                  <\/jats:p>","DOI":"10.1073\/pnas.061031898","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:44:19Z","timestamp":1027680259000},"page":"4089-4094","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":69,"title":["Suppression of ras-mediated transformation and inhibition of tumor growth and angiogenesis by anthrax lethal factor, a proteolytic inhibitor of multiple MEK pathways"],"prefix":"10.1073","volume":"98","author":[{"given":"N. S.","family":"Duesbery","sequence":"first","affiliation":[{"name":"Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand\r Rapids, MI 49503; Advanced BioScience Laboratories Basic\r Research Program, National Cancer Institute\u2013Frederick Cancer Research\r and Development Center, P.O. Box B, Frederick, MD 21702; and\r National Institute of Dental and Craniofacial\r Research, Building 30, Room 309, National Institutes of Health,\r Bethesda, MD 20892-4350"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"J.","family":"Resau","sequence":"additional","affiliation":[{"name":"Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand\r Rapids, MI 49503; Advanced BioScience Laboratories Basic\r Research Program, National Cancer Institute\u2013Frederick Cancer Research\r and Development Center, P.O. Box B, Frederick, MD 21702; and\r National Institute of Dental and Craniofacial\r Research, Building 30, Room 309, National Institutes of Health,\r Bethesda, MD 20892-4350"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"C. P.","family":"Webb","sequence":"additional","affiliation":[{"name":"Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand\r Rapids, MI 49503; Advanced BioScience Laboratories Basic\r Research Program, National Cancer Institute\u2013Frederick Cancer Research\r and Development Center, P.O. Box B, Frederick, MD 21702; and\r National Institute of Dental and Craniofacial\r Research, Building 30, Room 309, National Institutes of Health,\r Bethesda, MD 20892-4350"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S.","family":"Koochekpour","sequence":"additional","affiliation":[{"name":"Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand\r Rapids, MI 49503; Advanced BioScience Laboratories Basic\r Research Program, National Cancer Institute\u2013Frederick Cancer Research\r and Development Center, P.O. Box B, Frederick, MD 21702; and\r National Institute of Dental and Craniofacial\r Research, Building 30, Room 309, National Institutes of Health,\r Bethesda, MD 20892-4350"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"H.-M.","family":"Koo","sequence":"additional","affiliation":[{"name":"Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand\r Rapids, MI 49503; Advanced BioScience Laboratories Basic\r Research Program, National Cancer Institute\u2013Frederick Cancer Research\r and Development Center, P.O. Box B, Frederick, MD 21702; and\r National Institute of Dental and Craniofacial\r Research, Building 30, Room 309, National Institutes of Health,\r Bethesda, MD 20892-4350"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. H.","family":"Leppla","sequence":"additional","affiliation":[{"name":"Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand\r Rapids, MI 49503; Advanced BioScience Laboratories Basic\r Research Program, National Cancer Institute\u2013Frederick Cancer Research\r and Development Center, P.O. Box B, Frederick, MD 21702; and\r National Institute of Dental and Craniofacial\r Research, Building 30, Room 309, National Institutes of Health,\r Bethesda, MD 20892-4350"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"G. F.","family":"Vande Woude","sequence":"additional","affiliation":[{"name":"Van Andel Research Institute, 333 Bostwick Avenue, NE, Grand\r Rapids, MI 49503; Advanced BioScience Laboratories Basic\r Research Program, National Cancer Institute\u2013Frederick Cancer Research\r and Development Center, P.O. 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