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dc.contributor.authorOikari, S
dc.contributor.authorKettunen, T
dc.contributor.authorTiainen, S
dc.contributor.authorHäyrinen, J
dc.contributor.authorMasarwah, A
dc.contributor.authorSudah, M
dc.contributor.authorSutela, A
dc.contributor.authorVanninen, R
dc.contributor.authorTammi, M
dc.contributor.authorAuvinen, P
dc.date.accessioned2018-04-25T11:01:14Z
dc.date.available2018-04-25T11:01:14Z
dc.date.issued2018
dc.identifier.urihttps://erepo.uef.fi/handle/123456789/6549
dc.description.abstractIncreased uptake of glucose, a general hallmark of malignant tumors, leads to an accumulation of intermediate metabolites of glycolysis. We investigated whether the high supply of these intermediates promotes their flow into UDP-sugars, and consequently into hyaluronan, a tumor-promoting matrix molecule. We quantified UDP-N-Acetylglucosamine (UDP-GlcNAc) and UDP-glucuronic acid (UDP-GlcUA) in human breast cancer biopsies, the levels of enzymes contributing to their synthesis, and their association with the hyaluronan accumulation in the tumor. The content of UDP-GlcUA was 4 times, and that of UDP-GlcNAc 12 times higher in the tumors as compared to normal glandular tissue obtained from breast reductions. The surge of UDP-GlcNAc correlated with an elevated mRNA expression of glutamine-fructose-6-phosphate aminotransferase 2 (GFAT2), one of the key enzymes in the biosynthesis of UDP-GlcNAc, and the expression of GFAT1 was also elevated. The contents of both UDP-sugars strongly correlated with tumor hyaluronan levels. Interestingly, hyaluronan content did not correlate with the mRNA levels of the hyaluronan synthases (HAS1–3), thus emphasizing the role of the UDP-sugar substrates of these enzymes. The UDP-sugars showed a trend to higher levels in ductal vs. lobular cancer subtypes. The results reveal for the first time a dramatic increase of UDP-sugars in breast cancer, and suggest that their high supply drives the accumulation of hyaluronan, a known promoter of breast cancer and other malignancies. In general, the study shows how the disturbed glucose metabolism typical for malignant tumors can influence cancer microenvironment through UDP-sugars and hyaluronan.
dc.language.isoEN
dc.publisherElsevier BV
dc.relation.ispartofseriesMATRIX BIOLOGY
dc.relation.urihttp://dx.doi.org/10.1016/j.matbio.2017.12.015
dc.rightsCC BY-NC-ND https://creativecommons.org/licenses/by-nc-nd/4.0/
dc.subjectUDP-sugar
dc.subjectbreast cancer
dc.subjectUDP-N-Acetylglucosamine
dc.subjecthyaluronan
dc.subjectWarburg effect
dc.titleUDP-sugar accumulation drives hyaluronan synthesis in breast cancer
dc.description.versionfinal draft
dc.contributor.departmentSchool of Medicine / Dentistry
dc.contributor.departmentSchool of Medicine / Clinical Medicine,School of Medicine / Biomedicine
uef.solecris.id51982642en
dc.type.publicationTieteelliset aikakauslehtiartikkelit
dc.rights.accessrights© Elsevier B.V.
dc.relation.doi10.1016/j.matbio.2017.12.015
dc.description.reviewstatuspeerReviewed
dc.format.pagerange63-74
dc.relation.issn0945-053X
dc.relation.volume67
dc.type.okmA1
uef.solecris.openaccessEi


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