{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,25]],"date-time":"2026-09-25T17:25:55Z","timestamp":1790357155448,"version":"4.1.0"},"reference-count":36,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2017,4,3]],"date-time":"2017-04-03T00:00:00Z","timestamp":1491177600000},"content-version":"vor","delay-in-days":33,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/100002002","name":"Cancer Research Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100002002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cancer Science"],"published-print":{"date-parts":[[2017,3]]},"abstract":"<jats:p>T\u2010lymphokine\u2010activated killer cell\u2010originated protein kinase (<jats:styled-content style=\"fixed-case\">TOPK<\/jats:styled-content>) plays critical roles in cancer cell proliferation as well as maintenance of cancer stem cells (<jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>). Small cell lung cancer (<jats:styled-content style=\"fixed-case\">SCLC<\/jats:styled-content>) has\u00a0highly\u00a0aggressive phenotype<jats:italic>,<\/jats:italic> reveals early spread to distant sites,\u00a0and results in dismal prognosis with little effective treatment. In this study, we demonstrate that <jats:styled-content style=\"fixed-case\">TOPK<\/jats:styled-content> expression was highly upregulated in both <jats:styled-content style=\"fixed-case\">SCLC<\/jats:styled-content> cell lines and primary tumors. Similar to si<jats:styled-content style=\"fixed-case\">RNA<\/jats:styled-content>\u2010mediated <jats:styled-content style=\"fixed-case\">TOPK<\/jats:styled-content> knockdown effects, treatment with a potent <jats:styled-content style=\"fixed-case\">TOPK<\/jats:styled-content> inhibitor, <jats:styled-content style=\"fixed-case\">OTS<\/jats:styled-content>514, effectively suppressed growth of <jats:styled-content style=\"fixed-case\">SCLC<\/jats:styled-content> cell lines (<jats:styled-content style=\"fixed-case\">IC<\/jats:styled-content><jats:sub>50<\/jats:sub>; 0.4\u201342.6 <jats:styled-content style=\"fixed-case\">nM<\/jats:styled-content>) and led to their apoptotic cell death. <jats:styled-content style=\"fixed-case\">TOPK<\/jats:styled-content> inhibition caused cell morphologic changes in <jats:styled-content style=\"fixed-case\">SCLC<\/jats:styled-content> cells, elongation of intercellular bridges caused by cytokinesis defects or neuronal protrusions induced by neuronal differentiation in a subset of <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\u2010like <jats:styled-content style=\"fixed-case\">SCLC<\/jats:styled-content> cells. Treatment with <jats:styled-content style=\"fixed-case\">OTS<\/jats:styled-content>514 suppressed forkhead box protein M1 (<jats:styled-content style=\"fixed-case\">FOXM<\/jats:styled-content>1) activity, which was involved in stemness of <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>. Furthermore, <jats:styled-content style=\"fixed-case\">OTS<\/jats:styled-content>514 treatment reduced <jats:styled-content style=\"fixed-case\">CD<\/jats:styled-content>90\u2010positive <jats:styled-content style=\"fixed-case\">SCLC<\/jats:styled-content> cells and showed higher cytotoxic effect against lung sphere\u2010derived <jats:styled-content style=\"fixed-case\">CSC<\/jats:styled-content>\u2010like <jats:styled-content style=\"fixed-case\">SCLC<\/jats:styled-content> cells. Collectively, our results suggest that targeting <jats:styled-content style=\"fixed-case\">TOPK<\/jats:styled-content> is a promising approach for <jats:styled-content style=\"fixed-case\">SCLC<\/jats:styled-content> therapy.<\/jats:p>","DOI":"10.1111\/cas.13160","type":"journal-article","created":{"date-parts":[[2017,1,11]],"date-time":"2017-01-11T15:41:39Z","timestamp":1484149299000},"page":"488-496","source":"Crossref","is-referenced-by-count":31,"title":["<scp>TOPK<\/scp> (T\u2010<scp>LAK<\/scp> cell\u2010originated protein kinase) inhibitor exhibits growth suppressive effect on small cell lung cancer"],"prefix":"10.1111","volume":"108","author":[{"given":"Jae\u2010Hyun","family":"Park","sequence":"first","affiliation":[{"name":"Department of Medicine The University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hiroyuki","family":"Inoue","sequence":"additional","affiliation":[{"name":"Department of Medicine The University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taigo","family":"Kato","sequence":"additional","affiliation":[{"name":"Department of Medicine The University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Makda","family":"Zewde","sequence":"additional","affiliation":[{"name":"Department of Medicine The University of Chicago Chicago IL USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Takashi","family":"Miyamoto","sequence":"additional","affiliation":[{"name":"OncoTherapy Science Inc. 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