{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,9]],"date-time":"2026-07-09T16:08:38Z","timestamp":1783613318792,"version":"3.55.0"},"reference-count":52,"publisher":"Wiley","issue":"18","license":[{"start":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T00:00:00Z","timestamp":1630540800000},"content-version":"vor","delay-in-days":1,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Cancer Medicine"],"published-print":{"date-parts":[[2021,9]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rhabdomyosarcoma exhibits tumor\u2010specific energy metabolic changes that include the Warburg effect. Since targeting cancer metabolism is a promising therapeutic approach, we examined the antitumor effects of suppressing lipid metabolism in rhabdomyosarcoma. We suppressed lipid metabolism in rhabdomyosarcoma cells in vitro by administering an inhibitor of malonyl\u2010CoA decarboxylase, which increases malonyl\u2010CoA and decreases fatty acid oxidation. Suppression of lipid metabolism in rhabdomyosarcoma cells decreased cell proliferation by inducing cell cycle arrest. Metabolomic analysis showed an increase in glycolysis and inactivation of the pentose phosphate pathway. Immunoblotting analysis revealed upregulated expression of the autophagy marker LC3A\/B\u2010II due to increased phosphorylation of AMP\u2010activated protein kinase, a nutrient sensor. p21 protein expression level also increased. Inhibition of both lipid metabolism and autophagy suppressed tumor proliferation and increased apoptosis. In vivo studies involved injection of human Rh30 cells into the gastrocnemius muscle of 6\u2010week\u2010old female nude mice, which were divided into normal chow and low\u2010fat diet groups. The mice fed a low\u2010fat diet for 21 days showed reduced tumor growth compared to normal chow diet\u2010fed mice. Suppression of lipid metabolism disrupted the equilibrium of the cancer\u2010specific metabolism in rhabdomyosarcoma, resulting in a tumor growth\u2010inhibition effect. Therefore, the development of treatments focusing on the lipid dependence of rhabdomyosarcoma is highly promising.<\/jats:p>","DOI":"10.1002\/cam4.4185","type":"journal-article","created":{"date-parts":[[2021,9,2]],"date-time":"2021-09-02T11:46:09Z","timestamp":1630583169000},"page":"6442-6455","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Inhibition of lipid metabolism exerts antitumor effects on rhabdomyosarcoma"],"prefix":"10.1002","volume":"10","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8856-6804","authenticated-orcid":false,"given":"Satoshi","family":"Miyagaki","sequence":"first","affiliation":[{"name":"Department of Pediatrics Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3097-7480","authenticated-orcid":false,"given":"Ken","family":"Kikuchi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"},{"name":"Department of Pediatrics Uji Takeda Hospital Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jun","family":"Mori","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gary D.","family":"Lopaschuk","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Mazankowski Alberta Heart Institute University of Alberta Edmonton Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoko","family":"Iehara","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hajime","family":"Hosoi","sequence":"additional","affiliation":[{"name":"Department of Pediatrics Graduate School of Medical Science Kyoto Prefectural University of Medicine Kyoto Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2021,9,2]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pgen.1004107"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.3892\/or.2016.5213"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOP.0b013e32832b4171"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.4161\/cbt.51"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12098-017-2315-3"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.123.3191.309"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.18632\/oncotarget.6272"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tibs.2014.06.005"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1007\/s13238-014-0082-8"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1186\/1476-4598-7-79"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)67091-7"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1089\/nat.2017.0673"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.gde.2008.02.003"},{"key":"e_1_2_9_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2009.09.005"},{"key":"e_1_2_9_16_1","doi-asserted-by":"publisher","DOI":"10.1159\/000132446"},{"issue":"10","key":"e_1_2_9_17_1","first-page":"4119","article-title":"Pediatric rhabdomyosarcoma cell lines are resistant to Fas\u2010induced apoptosis and highly sensitive to TRAIL\u2010induced apoptosis","volume":"6","author":"Petak I","year":"2000","journal-title":"Clin Cancer Res"},{"issue":"202","key":"e_1_2_9_18_1","first-page":"1","article-title":"Cellular and molecular characteristics of established childhood soft\u2010tissue sarcoma cell lines","volume":"7","author":"Sugimoto T","year":"2019","journal-title":"J Cancer Res Ther Oncol"},{"issue":"1","key":"e_1_2_9_19_1","first-page":"41","article-title":"Insulin\u2010like growth factor\u2010I has different effects on myogenin induction and cell cycle progression in human alveolar and embryonal rhabdomyosarcoma cells","volume":"31","author":"Tsuchiya K","year":"2007","journal-title":"Int J Oncol"},{"key":"e_1_2_9_20_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2019.03.038"},{"key":"e_1_2_9_21_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.00018.2012"},{"key":"e_1_2_9_22_1","doi-asserted-by":"publisher","DOI":"10.2337\/db15-1145"},{"key":"e_1_2_9_23_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0086813"},{"key":"e_1_2_9_24_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.575464"},{"key":"e_1_2_9_25_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M601876200"},{"key":"e_1_2_9_26_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2407-12-154"},{"key":"e_1_2_9_27_1","doi-asserted-by":"publisher","DOI":"10.1002\/iub.1253"},{"key":"e_1_2_9_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0709747104"},{"key":"e_1_2_9_29_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308061100"},{"key":"e_1_2_9_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature09706"},{"key":"e_1_2_9_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbpb.2007.04.001"},{"key":"e_1_2_9_32_1","doi-asserted-by":"publisher","DOI":"10.3389\/fonc.2013.00183"},{"key":"e_1_2_9_33_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-08-2955"},{"key":"e_1_2_9_34_1","doi-asserted-by":"publisher","DOI":"10.1158\/2159-8290.CD-13-0639"},{"key":"e_1_2_9_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1204440"},{"key":"e_1_2_9_36_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M113.494328"},{"key":"e_1_2_9_37_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-cellbio-092910-154005"},{"key":"e_1_2_9_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.04.004"},{"key":"e_1_2_9_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncb2152"},{"key":"e_1_2_9_40_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M900301200"},{"key":"e_1_2_9_41_1","doi-asserted-by":"publisher","DOI":"10.1161\/RES.0b013e3182194c29"},{"key":"e_1_2_9_42_1","doi-asserted-by":"publisher","DOI":"10.4161\/auto.20586"},{"key":"e_1_2_9_43_1","doi-asserted-by":"publisher","DOI":"10.1101\/gad.287524.116"},{"key":"e_1_2_9_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-1054-3"},{"key":"e_1_2_9_45_1","doi-asserted-by":"publisher","DOI":"10.1111\/jcmm.13865"},{"key":"e_1_2_9_46_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-018-0799-z"},{"key":"e_1_2_9_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41420-018-0115-9"},{"issue":"1","key":"e_1_2_9_48_1","first-page":"359","article-title":"PFK15, a PFKFB3 antagonist, inhibits autophagy and proliferation in rhabdomyosarcoma cells","volume":"42","author":"Wang C","year":"2018","journal-title":"Int J Mol Med"},{"key":"e_1_2_9_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-019-1958-6"},{"key":"e_1_2_9_50_1","doi-asserted-by":"publisher","DOI":"10.1158\/1078-0432.CCR-18-0106"},{"key":"e_1_2_9_51_1","doi-asserted-by":"publisher","DOI":"10.1002\/JLB.4HI0517-210R"},{"key":"e_1_2_9_52_1","doi-asserted-by":"publisher","DOI":"10.3390\/molecules23081941"},{"key":"e_1_2_9_53_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12943-017-0646-3"}],"container-title":["Cancer Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4185","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/full-xml\/10.1002\/cam4.4185","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/cam4.4185","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,8,30]],"date-time":"2023-08-30T01:50:58Z","timestamp":1693360258000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/cam4.4185"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,9]]},"references-count":52,"journal-issue":{"issue":"18","published-print":{"date-parts":[[2021,9]]}},"alternative-id":["10.1002\/cam4.4185"],"URL":"https:\/\/doi.org\/10.1002\/cam4.4185","archive":["Portico"],"relation":{},"ISSN":["2045-7634","2045-7634"],"issn-type":[{"value":"2045-7634","type":"print"},{"value":"2045-7634","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,9]]},"assertion":[{"value":"2021-06-11","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-07-17","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2021-09-02","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}