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Identifying novel proteins regulated by different molecular weight HA may highlight novel therapeutic targets. Proteomics analysis was performed to identify novel proteins regulated by different molecular weight HA (27, 183 and 1000\u2009kDa) in ES\u20102 ovarian cancer cells over\u2010expressing Notch3 intra\u2010cellular domain. Our analyses identified sphingosine kinase 1 (SPHK1), a novel protein regulated by 183\u2010 and 1000\u2010kDa HA. Utilising online databases and high\u2010grade serous ovarian cancer (HGSOC) patient tissue microarray cohorts, we assessed the relationship between SPHK1 expression and ovarian cancer metastasis, recurrence and patient outcome. We assessed the effects of the HA synthesis inhibitor 4\u2010methylumbelliferone (4\u2010MU) on SPHK1 expression in ovarian cancer cells and HGSOC patient tissues using ex\u00a0vivo tissue explant assays. SPHK1 was significantly increased in ovarian cancer compared to normal tissues, elevated in metastatic and recurrent HGSOC tissues and associated with poor patient outcome. 4\u2010MU significantly inhibited SPHK1 expression in ovarian cancer cells (ES\u20102, CaOV3 and A2780) and HGSOC patient tissues. This study highlights a link between HA and SPHK1 expression in ovarian cancer. Our findings confirm an adverse effect on ovarian cancer prognosis. SPHK1 constitutes a novel promising target against ovarian cancer that warrants further investigation.<\/jats:p>","DOI":"10.1111\/jcmm.70574","type":"journal-article","created":{"date-parts":[[2025,5,12]],"date-time":"2025-05-12T23:59:40Z","timestamp":1747094380000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Identification of Sphingosine Kinase 1 as a Novel Protein Regulated by High Molecular Weight Hyaluronan in Ovarian Cancer"],"prefix":"10.1111","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5306-3468","authenticated-orcid":false,"given":"Zoe K.","family":"Price","sequence":"first","affiliation":[{"name":"Discipline of Obstetrics and Gynaecology Adelaide Medical School, University of Adelaide  Adelaide South Australia Australia"},{"name":"Robinson Research Institute University of Adelaide  Adelaide South Australia Australia"},{"name":"Department of Obstetrics and Gynecology Nagoya 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