ArticlebioRxiv : the preprint server for biology2026
A non-canonical EZH2/TRIM28 epigenetic axis drives heparan sulfate remodeling and melanoma metastasis.
Neil G Patel, Alexandra Drakaki, Farhan Valummel, Jack C Moore, Amrita Basu, Bin Hu, Xiaolin Dong, Peng Zhao, Mees Botman, Emily Spector and 5 more
Abstract readPreprint
In one paragraphArticle in bioRxiv : the preprint server for biology, 2026. 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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2 · The registryThe trial behind it
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4 · The recordCorrections and comments
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5 · Who and what moneyAuthors and funding
15 authors.
Neil G PatelComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.ORCID 0000-0001-7594-088X Alexandra DrakakiDepartment of Medical Biochemistry, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0009-0001-5496-7933 Farhan ValummelDepartment of Biochemistry and Molecular Biology, University of Georgia, Athens, Georgia 30602, United States.
Jack C MooreComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.ORCID 0000-0001-9739-5528 Amrita BasuComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.ORCID 0000-0002-9670-9908 Bin HuMassey Cancer Center, Virginia Commonwealth University; Richmond, VA, United States.
Xiaolin DongComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.ORCID 0009-0009-1698-1839 Peng ZhaoComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.
Mees BotmanDepartment of Medical Biochemistry, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Emily SpectorComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.
Mark C MochelDepartment of Pathology, Virginia Commonwealth University; Richmond, VA, United States.ORCID 0000-0001-7306-8813 Lance WellsComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.ORCID 0000-0003-4956-5363 Jennifer E KoblinskiMassey Cancer Center, Virginia Commonwealth University; Richmond, VA, United States.ORCID 0000-0002-7156-2030 Marten A HoeksemaDepartment of Medical Biochemistry, Amsterdam University Medical Center, University of Amsterdam, Amsterdam, The Netherlands.ORCID 0000-0001-5981-121X Ryan J WeissComplex Carbohydrate Research Center, University of Georgia, Athens, Georgia 30602, United States.ORCID 0000-0002-4563-6075 Funding
Virus Vector Shared ResourceP30CA016059 · NCI · VIRGINIA COMMONWEALTH UNIVERSITY · PI Keri R Maher · 1985 to 2026
$51.0MInvestigating the molecular mechanisms of glycosaminoglycan assemblyR35GM150736 · NIGMS · UNIVERSITY OF GEORGIA · PI Ryan Joseph Weiss · 2023 to 2026
$1.5MGlycoscience Training ProgramT32GM107004 · NIGMS · UNIVERSITY OF GEORGIA · PI AMSTER, I JONATHAN, HALTIWANGER, ROBERT S. · 2014 to 2021
$1.3MNCI NIH HHS P30 CA016059NIGMS NIH HHS R35 GM150736NIGMS NIH HHS T32 GM107004
6 · The paper itselfAbstract
Melanoma progression and metastasis are driven not only by oncogenic alterations but also by epigenetic programs that dynamically remodel the tumor microenvironment. Heparan sulfate (HS) proteoglycans are key extracellular matrix components that integrate growth factor signaling, cell-matrix interactions, and migratory behavior by controlling ligand availability and receptor engagement, yet how chromatin-associated factors regulate HS remodeling in cancer remains poorly defined. Here, we identify the histone methyltransferase EZH2 as a key regulator of HS biosynthesis in melanoma. Integrated bioinformatic and genomic analyses revealed enrichment of EZH2 and additional Polycomb Repressive Complex (PRC) factors at regulatory regions of HS biosynthetic genes. CRISPR-mediated loss of EZH2 altered expression of multiple HS-modifying enzymes, most notably the secreted endosulfatases SULF1 and SULF2, resulting in enhanced HS 6-
Indexed as
epigenetic regulationEZH2glycosaminoglycansheparan sulfatemelanomametastasisSULF1transcriptionTRIM28
Identifiers
PMID41648528
PMCPMC12871662
What Socratic holds
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LicenceCC BY
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