{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,2]],"date-time":"2026-09-02T16:49:45Z","timestamp":1788367785619,"version":"build-2803163510"},"reference-count":88,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2025,5,26]],"date-time":"2025-05-26T00:00:00Z","timestamp":1748217600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Institutes of Health","award":["R15CA167476"],"award-info":[{"award-number":["R15CA167476"]}]},{"name":"National Institutes of Health","award":["P20 GM103424-11"],"award-info":[{"award-number":["P20 GM103424-11"]}]},{"name":"National Institutes of Health","award":["Delta-CRP 22, 23"],"award-info":[{"award-number":["Delta-CRP 22, 23"]}]},{"DOI":"10.13039\/100000057","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R15CA167476"],"award-info":[{"award-number":["R15CA167476"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["P20 GM103424-11"],"award-info":[{"award-number":["P20 GM103424-11"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000057","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["Delta-CRP 22, 23"],"award-info":[{"award-number":["Delta-CRP 22, 23"]}],"id":[{"id":"10.13039\/100000057","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Delta Collaborative Research Program","award":["R15CA167476"],"award-info":[{"award-number":["R15CA167476"]}]},{"name":"Delta Collaborative Research Program","award":["P20 GM103424-11"],"award-info":[{"award-number":["P20 GM103424-11"]}]},{"name":"Delta Collaborative Research Program","award":["Delta-CRP 22, 23"],"award-info":[{"award-number":["Delta-CRP 22, 23"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Emergent cancer drug resistance and further metastasis can mainly be attributed to altered expression levels and functional activities of multiple genes of cancer cells under chemotherapy. In response to challenge with anticancer drugs, enhanced ceramide glycosylation catalyzed by glucosylceramide synthase (GCS) confers drug resistance and enrichment with cancer stem cells. p53 mutations, which gain function in tumor progression, are prevalently extant in ovarian cancers. Via integrated gene expression assessments, we characterized GCS-responsive genes in ovarian cancer cells treated with dactinomycin. NCI\/ADR-RES cells dominantly expressed a p53 mutant (7 aa deleted in exon-5) and displayed anti-apoptosis; however, silencing GCS expression rendered these cells sensitive to dactinomycin-induced apoptosis. Microarray analyses of NCI\/ADR-RES and its GCS transfected sublines found that elevated GCS expression or ceramide glycosylation was associated with altered expression of 41 genes, notably coding for ABCB1, FGF2, ALDH1A3, apolipoprotein E, laminin 2, chemokine ligands, and IL6, with cellular resistance to induced apoptosis and enrichment with cancer stem cells, promoting cancer progression. These findings were further corroborated through integrated genomic analyses of ovarian cancer from The Cancer Genome Atlas (TCGA) and cancer resistance to platinum-based chemotherapy. Altogether, our present study indicates that altered ceramide glycosylation can modulate expression of these GCS-responsive genes and alter cancer cell attributes under chemotherapy.<\/jats:p>","DOI":"10.3390\/ijms26115112","type":"journal-article","created":{"date-parts":[[2025,5,28]],"date-time":"2025-05-28T03:52:08Z","timestamp":1748404328000},"page":"5112","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Glucosylceramide Synthase, a Key Enzyme in Sphingolipid Metabolism, Regulates Expression of Genes Accounting for Cancer Drug Resistance"],"prefix":"10.3390","volume":"26","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-2359-4481","authenticated-orcid":false,"given":"Md Saqline","family":"Mostaq","sequence":"first","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana at Monroe, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Biomedical Affairs and Research, Edward Via College of Osteopathic Medicine, Monroe, LA 71203, USA"},{"name":"Department of Biomedical Sciences and Pathobiology, Virginia Tech, VA-MD Regional College of Veterinary Medicine, Blacksburg, VA 24060, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gauri A.","family":"Patwardhan","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana at Monroe, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2122-2265","authenticated-orcid":false,"given":"Yunfeng","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Toxicology and Neuroscience, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Runhua","family":"Shi","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Louisiana State University Health Sciences Center, Shreveport, LA 71103, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7968-0162","authenticated-orcid":false,"given":"Yong-Yu","family":"Liu","sequence":"additional","affiliation":[{"name":"School of Basic Pharmaceutical and Toxicological Sciences, University of Louisiana at Monroe, Monroe, LA 71201, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,5,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1074\/jbc.274.2.1140","article-title":"Expression of glucosylceramide synthase, converting ceramide to glucosylceramide, confers adriamycin resistance in human breast cancer cells","volume":"274","author":"Liu","year":"1999","journal-title":"J. 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