{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,24]],"date-time":"2026-09-24T11:06:02Z","timestamp":1790247962160,"version":"4.1.0"},"reference-count":70,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T00:00:00Z","timestamp":1790121600000},"content-version":"vor","delay-in-days":22,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/100032645","name":"Hevolution Foundation","doi-asserted-by":"publisher","award":["HF\u2010GRO\u201023\u20101199172\u201046"],"award-info":[{"award-number":["HF\u2010GRO\u201023\u20101199172\u201046"]}],"id":[{"id":"10.13039\/100032645","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100032645","name":"Hevolution Foundation","doi-asserted-by":"publisher","award":["NIA R01AG064003"],"award-info":[{"award-number":["NIA R01AG064003"]}],"id":[{"id":"10.13039\/100032645","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["FASEB BioAdvances"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Intracellular sphingolipids play a complex role in the survival and migration of oral squamous cell carcinoma (OSCC). For instance, dihydroceramide and ceramide sphingolipids suppress proliferation, whereas sphingosine\u20101\u2010phosphate (S\u20101\u2010P) promotes it. The balance between ceramide\/S\u20101\u2010P is critically regulated by the ceramide\u2010hydrolyzing enzyme, acid ceramidase (aCDase), in OSCC. Indeed, aCDase mRNA expression is significantly upregulated compared with that in healthy epithelial cells. Our group identified that\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>Porphyromonas gingivalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    synthesizes a structurally unique phosphoglycerol\u2010isoC17:0\u2010dihydroceramide (PGDHC) sphingolipid. Our understanding of whether PGDHC modulates the critical ceramide\/S\u20101\u2010P balance and aCDase levels in OSCC remains limited. The effects of PGDHC on human OSCC cell lines and healthy oral epithelial cells were evaluated in\u00a0vitro using conventional assays combined with untargeted and ceramide\u2010targeted lipidomic screenings. Human tongue oral malignancy and the adjacent normal tissue from the same patient were also evaluated for the prevalence of anti\u2010\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    IgG. Additionally, aCDase levels were evaluated in OSCC cell lines, clinical oral malignancy samples, and mouse models of 4\u2010nitroquinoline\u20101\u2010oxide (4\u2010NQO)\u2010induced OSCC. We identified the accelerated prevalence of aCDase in clinical and experimental malignant lesions. In contrast, we observed a lower prevalence of PGDHC\u2010producing\n                    <jats:styled-content style=\"fixed-case\">\n                      <jats:italic>P. gingivalis<\/jats:italic>\n                    <\/jats:styled-content>\n                    in malignant lesions than in adjacent normal tissue. Indeed, our in\u00a0vitro observations further demonstrated that PGDHC accelerates the accumulation of C16:0 dihydroceramide in OSCC by inhibiting acid ceramidase\/ASAH1 mRNA expression. Altogether, PGDHC alters sphingolipid metabolism in human OSCC cells through the acid ceramidase\/dihydroceramide axis. This finding lays the foundation for developing novel therapeutic strategies for oral cancer using PGDHC as a novel class of OSCC\u2010suppressing compounds.\n                  <\/jats:p>","DOI":"10.1096\/fba.2026-00032","type":"journal-article","created":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T14:47:18Z","timestamp":1790174838000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<i>Porphyromonas gingivalis<\/i>\n                    \u2010Derived Phosphoglycerol\u2010\n                    <scp>isoC17<\/scp>\n                    :0\u2010Dihydroceramide Reprograms Sphingolipid Metabolism in Human\n                    <scp>OECM<\/scp>\n                    \u20101 Oral Squamous Cell Carcinoma Cells"],"prefix":"10.1096","volume":"8","author":[{"given":"Chiaki","family":"Yamada","sequence":"first","affiliation":[{"name":"Department of Biomedical and Applied Science Indiana University School of Dentistry  Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Richard L. Roudebush VA Medical Center  Indianapolis Indiana USA"},{"name":"Indiana University Melvin and Bren Simon Comprehensive Cancer Center  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anny","family":"Ho","sequence":"additional","affiliation":[{"name":"Institute for Neuro\u2010Immune Medicine Nova Southeastern University  Fort Lauderdale Florida USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Natasha","family":"Sanz","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Applied Science Indiana University School of Dentistry  Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gang","family":"Peng","sequence":"additional","affiliation":[{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Department of Medical and Molecular Genetics Indiana University School of Medicine  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruijuan","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stony Brook Cancer Center, Renaissance School of Medicine The State University of New York at Stony Brook  Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cungui","family":"Mao","sequence":"additional","affiliation":[{"name":"Department of Medicine, Stony Brook Cancer Center, Renaissance School of Medicine The State University of New York at Stony Brook  Stony Brook New York USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Otolaryngology\u2010Head &amp; Neck Surgery, School of Medicine Indiana University  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatemeh","family":"Momen\u2010Heravi","sequence":"additional","affiliation":[{"name":"Department of Orofacial Sciences, School of Dentistry University of California San Francisco  San Francisco California USA"},{"name":"Cancer Biology and Immunology Laboratory, School of Dentistry University of California San Francisco  San Francisco California USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C.","family":"Edwards","sequence":"additional","affiliation":[{"name":"Department of Oral Pathology, Medicine and Radiology Indiana University School of Dentistry  Indianapolis Indiana USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank","family":"Nichols","sequence":"additional","affiliation":[{"name":"Department of Oral Health and Diagnostic Sciences University of Connecticut School of Dental Medicine  Farmington Connecticut USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9827-7347","authenticated-orcid":false,"given":"Alexandru","family":"Movila","sequence":"additional","affiliation":[{"name":"Department of Biomedical and Applied Science Indiana University School of Dentistry  Indianapolis Indiana USA"},{"name":"Indiana Center for Musculoskeletal Health Indiana University School of Medicine  Indianapolis Indiana USA"},{"name":"Richard L. 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