Evidence map›Paper›PMID 26883802›Full record

ArticleCellular and molecular life sciences : CMLS2016

UDP-sugar substrates of HAS3 regulate its O-GlcNAcylation, intracellular traffic, extracellular shedding and correlate with melanoma progression.

Ashik Jawahar Deen, Uma Thanigai Arasu, Sanna Pasonen-Seppänen, Antti Hassinen, Piia Takabe, Sara Wojciechowski, Riikka Kärnä, Kirsi Rilla, Sakari Kellokumpu, Raija Tammi and 2 more

Open access · greenAbstract read
In one paragraph

Article in Cellular and molecular life sciences : CMLS, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.

0numbers the graph read from it
0cells of the map it votes in
32citing papers in PubMed
4.2field-weighted citation impact, top 6% of its field
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

32 citing papers in PubMed, 53 citations in OpenAlex.

  1. Review
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  11. Cells · 2023
    Review
  12. Article
  13. Review
  14. Review
  15. Review
  16. Article
  17. Cell Energy Metabolism and Hyaluronan Synthesis.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021
    Review
  18. Integration of Sugar Metabolism and Proteoglycan Synthesis by UDP-glucose Dehydrogenase.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2021
    Review
  19. Article
  20. Review
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

12 authors at 2 institutions in 1 country.

Ashik Jawahar DeenInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland. ashik.jawahardeen@uef.fi.
Uma Thanigai ArasuInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Sanna Pasonen-SeppänenInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Antti HassinenFaculty of Biochemistry and Molecular Medicine, University of Oulu, 90014, Oulu, Finland.
Piia TakabeInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Sara WojciechowskiA. I. Virtanen Institute for Molecular Sciences, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Riikka KärnäInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Kirsi RillaInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Sakari KellokumpuFaculty of Biochemistry and Molecular Medicine, University of Oulu, 90014, Oulu, Finland.
Raija TammiInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Markku TammiInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland.
Sanna OikariInstitute of Biomedicine, School of Medicine, University of Eastern Finland, 70210, Kuopio, Finland. sanna.oikari@uef.fi.
University of Eastern Finland · FIUniversity of Oulu · FI

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Hyaluronan content is a powerful prognostic factor in many cancer types, but the molecular basis of its synthesis in cancer still remains unclear. Hyaluronan synthesis requires the transport of hyaluronan synthases (HAS1-3) from Golgi to plasma membrane (PM), where the enzymes are activated. For the very first time, the present study demonstrated a rapid recycling of HAS3 between PM and endosomes, controlled by the cytosolic levels of the HAS substrates UDP-GlcUA and UDP-GlcNAc. Depletion of UDP-GlcNAc or UDP-GlcUA shifted the balance towards HAS3 endocytosis, and inhibition of hyaluronan synthesis. In contrast, UDP-GlcNAc surplus suppressed endocytosis and lysosomal decay of HAS3, favoring its retention in PM, stimulating hyaluronan synthesis, and HAS3 shedding in extracellular vesicles. The concentration of UDP-GlcNAc also controlled the level of O-GlcNAc modification of HAS3. Increasing O-GlcNAcylation reproduced the effects of UDP-GlcNAc surplus on HAS3 trafficking, while its suppression showed the opposite effects, indicating that O-GlcNAc signaling is associated to UDP-GlcNAc supply. Importantly, a similar correlation existed between the expression of GFAT1 (the rate limiting enzyme in UDP-GlcNAc synthesis) and hyaluronan content in early and deep human melanomas, suggesting the association of UDP-sugar metabolism in initiation of melanomagenesis. In general, changes in glucose metabolism, realized through UDP-sugar contents and O-GlcNAc signaling, are important in HAS3 trafficking, hyaluronan synthesis, and correlates with melanoma progression.

Indexed as

AcetylglucosamineAcylationAnimalsCell LineCell Line, TumorChlorocebus aethiopsCOS CellsDisease ProgressionEndocytosisGlucuronosyltransferaseHumansHyaluronan SynthasesHyaluronic AcidMelanomaProtein TransportSkinAcetylglucosamineGlucuronosyltransferaseHAS1 protein, humanHAS3 protein, humanHyaluronan SynthasesHyaluronic AcidUridine Diphosphate N-AcetylglucosamineUridine Diphosphate Sugars4MUGlucosamineGNPDAMannoseOGTUGDH

Identifiers

PMID26883802
PMCPMC11108457
OpenAlexW2278423251

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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 OpenQuestion graph.