{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:36:01Z","timestamp":1793162161225,"version":"4.5.0"},"reference-count":42,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,10,16]],"date-time":"2026-10-16T00:00:00Z","timestamp":1792108800000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T00:00:00Z","timestamp":1790812800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100000050","name":"National Heart, Lung, and Blood Institute","doi-asserted-by":"publisher","award":["R01HL167133A1"],"award-info":[{"award-number":["R01HL167133A1"]}],"id":[{"id":"10.13039\/100000050","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Reports"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Atypical teratoid\/rhabdoid tumors (ATRTs) are aggressive pediatric CNS malignancies with &lt;\u200930% 5\u2010year survival despite multimodal therapy. No prior studies have explored ferroptosis induction in ATRT.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>\n                      To determine whether GPR68 inhibition by ogremorphin (OGM) induces\n                      <jats:italic>ATF4<\/jats:italic>\n                      \u2010dependent ferroptosis in ATRT cell lines and whether SLC7A11 blockade (erastin, ERA) confers similar sensitivity.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      CHLA\u201002\u2010ATRT and CHLA\u201006\u2010ATRT cell lines were treated with OGM or ERA. Viability (CellTiter\u2010Glo), GSH levels (GSH\u2010Glo), lipid peroxidation (BODIPY 581\/591 C11), and gene expression (qRT\u2010PCR:\n                      <jats:italic>ATF4<\/jats:italic>\n                      ,\n                      <jats:italic>HMOX1<\/jats:italic>\n                      ,\n                      <jats:italic>SLC7A11<\/jats:italic>\n                      ,\n                      <jats:italic>TFRC<\/jats:italic>\n                      ) were assessed. Genetic validation used GPR68\/ATF4 shRNA, overexpression, and an\n                      <jats:italic>ATF4<\/jats:italic>\n                      luciferase reporter. Statistics: Student's\n                      <jats:italic>t<\/jats:italic>\n                      \u2010test with Bonferroni correction (R 4.4.0).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Both cell lines were sensitive to OGM\u2010 and ERA\u2010induced ferroptosis, with CHLA\u201002\u2010ATRT significantly more responsive to OGM than ERA. OGM\/ERA depleted GSH, increased lipid peroxidation, and upregulated\n                      <jats:italic>ATF4<\/jats:italic>\n                      ,\n                      <jats:italic>HMOX1<\/jats:italic>\n                      , and\n                      <jats:italic>SLC7A11<\/jats:italic>\n                      mRNA expression. OGM induced\n                      <jats:italic>TFRC<\/jats:italic>\n                      in both cell lines; high\u2010dose ERA upregulated\n                      <jats:italic>TFRC<\/jats:italic>\n                      in CHLA\u201002\u2010ATRT only. GPR68 knockdown reduced viability, while overexpression or Ogerin increased proliferation. OGM activated\n                      <jats:italic>ATF4<\/jats:italic>\n                      transcription, and\n                      <jats:italic>ATF4<\/jats:italic>\n                      overexpression decreased cell survival.\n                      <jats:italic>ATF4<\/jats:italic>\n                      knockdown rescued OGM\u2010treated cells.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      GPR68 inhibition triggers\n                      <jats:italic>ATF4<\/jats:italic>\n                      \u2010dependent ferroptosis in ATRT. SLC7A11 blockade by ERA paralleled the effects of ferroptosis by OGM. These data establish a novel therapeutic strategy with strong translational potential.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1002\/cnr2.70719","type":"journal-article","created":{"date-parts":[[2026,10,17]],"date-time":"2026-10-17T03:28:47Z","timestamp":1792207727000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>GPR68<\/scp>\n                    Inhibition Induces Ferroptosis in Atypical Teratoid Rhabdoid Tumors"],"prefix":"10.1002","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2621-6259","authenticated-orcid":false,"given":"Leif R.","family":"Neitzel","sequence":"first","affiliation":[{"name":"Department of Medicine Michigan State University College of Human Medicine  East Lansing Michigan USA"},{"name":"Henry Ford Health\u2009+\u2009Michigan State Health Sciences  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0424-8252","authenticated-orcid":false,"given":"Charles C.","family":"Hong","sequence":"additional","affiliation":[{"name":"Department of Medicine Michigan State University College of Human Medicine  East Lansing Michigan USA"},{"name":"Henry Ford Health\u2009+\u2009Michigan State Health Sciences  Detroit Michigan USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,16]]},"reference":[{"key":"e_1_2_14_2_1","doi-asserted-by":"publisher","DOI":"10.2147\/CMAR.S83472"},{"key":"e_1_2_14_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00401\u2010016\u20101545\u20101"},{"key":"e_1_2_14_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nov264"},{"key":"e_1_2_14_5_1","doi-asserted-by":"publisher","DOI":"10.1200\/JCO.2004.07.073"},{"key":"e_1_2_14_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/nou090"},{"key":"e_1_2_14_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.25540"},{"key":"e_1_2_14_8_1","doi-asserted-by":"publisher","DOI":"10.1007\/s004010051149"},{"key":"e_1_2_14_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.27373"},{"key":"e_1_2_14_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijpam.2020.06.004"},{"key":"e_1_2_14_11_1","doi-asserted-by":"publisher","DOI":"10.4103\/0973\u20101482.174536"},{"key":"e_1_2_14_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/neuonc\/noz235"},{"key":"e_1_2_14_13_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060\u2010016\u20102353\u20100"},{"key":"e_1_2_14_14_1","doi-asserted-by":"publisher","DOI":"10.3171\/2019.4.PEDS19113"},{"key":"e_1_2_14_15_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.28022"},{"key":"e_1_2_14_16_1","doi-asserted-by":"publisher","DOI":"10.3171\/2019.9.PEDS19367"},{"key":"e_1_2_14_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/cam4.741"},{"key":"e_1_2_14_18_1","doi-asserted-by":"publisher","DOI":"10.1002\/cncr.26684"},{"key":"e_1_2_14_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ejca.2011.09.005"},{"key":"e_1_2_14_20_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2018.00567"},{"key":"e_1_2_14_21_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11060\u2010020\u201003639\u2010w"},{"key":"e_1_2_14_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.acr.2025.08.007"},{"key":"e_1_2_14_23_1","doi-asserted-by":"publisher","DOI":"10.1097\/00043426\u2010200206000\u201000004"},{"key":"e_1_2_14_24_1","doi-asserted-by":"publisher","DOI":"10.1002\/pbc.23236"},{"key":"e_1_2_14_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijrobp.2005.10.001"},{"key":"e_1_2_14_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598\u2010025\u201088357\u2010x"},{"key":"e_1_2_14_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40164\u2010023\u201000468\u20101"},{"key":"e_1_2_14_28_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2026.1808752"},{"key":"e_1_2_14_29_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13104\u2010024\u201006900\u2010x"},{"key":"e_1_2_14_30_1","doi-asserted-by":"publisher","DOI":"10.17912\/micropub.biology.001524"},{"key":"e_1_2_14_31_1","doi-asserted-by":"publisher","DOI":"10.46439\/cancerbiology.5.066"},{"key":"e_1_2_14_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.celrep.2017.02.006"},{"key":"e_1_2_14_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01905"},{"key":"e_1_2_14_34_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20040840"},{"key":"e_1_2_14_35_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10495\u2010006\u20109789\u20101"},{"key":"e_1_2_14_36_1","doi-asserted-by":"publisher","DOI":"10.1016\/B978\u20100\u201012\u2010397927\u20108.00004\u2010X"},{"key":"e_1_2_14_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.humimm.2022.01.014"},{"key":"e_1_2_14_38_1","doi-asserted-by":"publisher","DOI":"10.1186\/1475\u20102867\u201013\u201089"},{"key":"e_1_2_14_39_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10585\u2010019\u201009990\u20101"},{"key":"e_1_2_14_40_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2013.00354"},{"key":"e_1_2_14_41_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev\u2010physiol\u2010021119\u2010034627"},{"key":"e_1_2_14_42_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.3078"},{"key":"e_1_2_14_43_1","doi-asserted-by":"publisher","DOI":"10.1016\/s1097\u20102765(00)00108\u20108"}],"container-title":["Cancer Reports"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70719","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cnr2.70719","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cnr2.70719","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,28]],"date-time":"2026-10-28T04:02:29Z","timestamp":1793160149000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cnr2.70719"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10]]},"references-count":42,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2026,10]]}},"alternative-id":["10.1002\/cnr2.70719"],"URL":"https:\/\/doi.org\/10.1002\/cnr2.70719","archive":["Portico"],"relation":{},"ISSN":["2573-8348","2573-8348"],"issn-type":[{"value":"2573-8348","type":"print"},{"value":"2573-8348","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10]]},"assertion":[{"value":"2025-12-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-01","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-16","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e70719"}}