Evidence mapPaperPMID 40356021Full record

ArticleJournal of cellular and molecular medicine2025

Identification of Sphingosine Kinase 1 as a Novel Protein Regulated by High Molecular Weight Hyaluronan in Ovarian Cancer.

Zoe K Price, Noor A Lokman, Jessica Morrison, Sisanda N Mhlanga, Mai Sugiyama, Yoshihiro Koya, Lorena T Davies, Stuart M Pitson, Martin K Oehler, Melissa R Pitman and 3 more

Abstract read
In one paragraph

Article in Journal of cellular and molecular medicine, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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0cells of the map it votes in
0citing papers in PubMed
field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Zoe K PriceDiscipline of Obstetrics and Gynaecology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.ORCID 0000-0001-5306-3468
Noor A LokmanDiscipline of Obstetrics and Gynaecology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Jessica MorrisonDiscipline of Obstetrics and Gynaecology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Sisanda N MhlangaDiscipline of Obstetrics and Gynaecology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Mai SugiyamaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Yoshihiro KoyaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Lorena T DaviesCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia.
Stuart M PitsonCentre for Cancer Biology, University of South Australia and SA Pathology, Adelaide, South Australia, Australia.
Martin K OehlerDiscipline of Obstetrics and Gynaecology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.
Melissa R PitmanRobinson Research Institute, University of Adelaide, Adelaide, South Australia, Australia.
Masato YoshiharaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Hiroaki KajiyamaDepartment of Obstetrics and Gynecology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Carmela RicciardelliDiscipline of Obstetrics and Gynaecology, Adelaide Medical School, University of Adelaide, Adelaide, South Australia, Australia.

Funding

Cancer Council South AustraliaJapan Society for the Promotion of Science London JSPS21K16788Japan Society for the Promotion of Science London JSPS21KK0296Ovarian Cancer Research FoundationUniversity of Adelaide
6 · The paper itself

Abstract

The effects of hyaluronan (HA) in cancer are widely studied; however, the role of different molecular weight HA is poorly understood. 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 kDa) in ES-2 ovarian cancer cells over-expressing Notch3 intra-cellular domain. Our analyses identified sphingosine kinase 1 (SPHK1), a novel protein regulated by 183- and 1000-kDa HA. Utilising online databases and high-grade 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-methylumbelliferone (4-MU) on SPHK1 expression in ovarian cancer cells and HGSOC patient tissues using ex vivo 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-MU significantly inhibited SPHK1 expression in ovarian cancer cells (ES-2, 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.

Indexed as

Hyaluronic AcidOvarian NeoplasmsPhosphotransferases (Alcohol Group Acceptor)Cell Line, TumorFemaleGene Expression Regulation, NeoplasticHumansHymecromoneMiddle AgedMolecular WeightNeoplasm Recurrence, LocalPrognosisSphingosine KinaseHyaluronic AcidHymecromonePhosphotransferases (Alcohol Group Acceptor)Sphingosine Kinase4‐methylumbelliferonehyaluronanNotch3ovarian cancerSPHK1

Identifiers

PMID40356021
PMCPMC12069020

What Socratic holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.