{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T19:12:06Z","timestamp":1792091526171,"version":"4.4.0"},"reference-count":56,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2021,1,10]],"date-time":"2021-01-10T00:00:00Z","timestamp":1610236800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["16K11125"],"award-info":[{"award-number":["16K11125"]}],"id":[{"id":"10.13039\/501100001691","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":[[2021,2]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Regulation of sphingolipid metabolism plays a role in cellular homeostasis, and dysregulation of these pathways is involved in cancer progression. Previously, our reports identified ceramide as an anti\u2010metastatic lipid. In the present study, we investigated the biochemical alterations in ceramide\u2010centered metabolism of sphingolipids that were associated with metastatic potential. We established metastasis\u2010prone sublines of SKOV3 ovarian cancer cells using an in vivo selection method. These cells showed decreases in ceramide levels and ceramide synthase (CerS) 2 expression. Moreover, CerS2 downregulation in ovarian cancer cells promoted metastasis in vivo and potentiated cell motility and invasiveness. Moreover, CerS2 knock\u2010in suppressed the formation of lamellipodia required for cell motility in this cell line. In order to define specific roles of ceramide species in cell motility controlled by CerS2, the effect of exogenous long\u2010 and very long\u2010chain ceramide species on the formation of lamellipodia was evaluated. Treatment with distinct ceramides increased cellular ceramides and had inhibitory effects on the formation of lamellipodia. Interestingly, blocking the recycling pathway of ceramides by a CerS inhibitor was ineffective in the suppression of exogenous C\n                    <jats:sub>24:1<\/jats:sub>\n                    \u2010ceramide for the formation of lamellipodia. These results suggested that C\n                    <jats:sub>24:1<\/jats:sub>\n                    \u2010ceramide, a CerS2 metabolite, predominantly suppresses the formation of lamellipodia without the requirement for deacylation\/reacylation. Moreover, knockdown of neutral ceramidase suppressed the formation of lamellipodia concomitant with upregulation of C\n                    <jats:sub>24:1<\/jats:sub>\n                    \u2010ceramide. Collectively, the CerS2\u2010C\n                    <jats:sub>24:1<\/jats:sub>\n                    \u2010ceramide axis, which may be countered by neutral ceramidase, is suggested to limit cell motility and metastatic potential. These findings may provide insights that lead to further development of ceramide\u2010based therapy and biomarkers for metastatic ovarian cancer.\n                  <\/jats:p>","DOI":"10.1096\/fj.202001504rr","type":"journal-article","created":{"date-parts":[[2021,1,14]],"date-time":"2021-01-14T22:13:26Z","timestamp":1610662406000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Ceramide synthase 2\u2010C\n                    <sub>24:1<\/sub>\n                    \u2010ceramide axis limits the metastatic potential of ovarian cancer cells"],"prefix":"10.1096","volume":"35","author":[{"given":"Xuewei","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology Tohoku University Graduate School of Medicine Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wataru","family":"Sakamoto","sequence":"additional","affiliation":[{"name":"Department of 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Molecular Biology Virginia Commonwealth University Richmond VA USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshiro","family":"Okazaki","sequence":"additional","affiliation":[{"name":"Medical Research Institute Kanazawa Medical University Ishikawa Japan"},{"name":"Department of Hematology and Immunology Kanazawa Medical University Ishikawa Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nobuo","family":"Yaegashi","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology Tohoku University Graduate School of Medicine Miyagi Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3349-3369","authenticated-orcid":false,"given":"Yusuf A.","family":"Hannun","sequence":"additional","affiliation":[{"name":"Department of Medicine Stony Brook Cancer Center Stony Brook NY USA"},{"name":"Stony Brook Cancer Center Stony Brook University Stony Brook NY USA"},{"name":"Department 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