Dietary supplements such as vitamins and minerals are widely used in the hope of improving health but may have unidentified risks and side effects. In particular, a pathogenic link between dietary supplements and specific oncogenes remains unknown. Here we report that chondroitin-4-sulfate (CHSA), a natural glycosaminoglycan approved as a dietary supplement used for osteoarthritis, selectively promotes the tumor growth potential of BRAF V600E-expressing human melanoma cells in patient- and cell line-derived xenograft mice and confers resistance to BRAF inhibitors. Mechanistically, chondroitin sulfate glucuronyltransferase (CSGlcA-T) signals through its product CHSA to enhance casein kinase 2 (CK2)-PTEN binding and consequent phosphorylation and inhibition of PTEN, which requires CHSA chains and is essential to sustain AKT activation in BRAF V600E-expressing melanoma cells. However, this CHSA-dependent PTEN inhibition is dispensable in cancer cells expressing mutant NRAS or PI3KCA, which directly activate the PI3K-AKT pathway. These results suggest that dietary supplements may exhibit oncogene-dependent pro-tumor effects.
Pubmed ID: 29547721 RIS Download
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View all literature mentionsNon-profit plasmid repository dedicated to helping scientists around the world share high-quality plasmids. Facilitates archiving and distributing DNA-based research reagents and associated data to scientists worldwide. Repository contains over 65,000 plasmids, including special collections on CRISPR, fluorescent proteins, and ready-to-use viral preparations. There is no cost for scientists to deposit plasmids, which saves time and money associated with shipping plasmids themselves. All plasmids are fully sequenced for validation and sequencing data is openly available. We handle the appropriate Material Transfer Agreements (MTA) with institutions, facilitating open exchange and offering intellectual property and liability protection for depositing scientists. Furthermore, we curate free educational resources for the scientific community including a blog, eBooks, video protocols, and detailed molecular biology resources.
View all literature mentionsInternational database for laboratory mouse. Data offered by The Jackson Laboratory includes information on integrated genetic, genomic, and biological data. MGI creates and maintains integrated representation of mouse genetic, genomic, expression, and phenotype data and develops reference data set and consensus data views, synthesizes comparative genomic data between mouse and other mammals, maintains set of links and collaborations with other bioinformatics resources, develops and supports analysis and data submission tools, and provides technical support for database users. Projects contributing to this resource are: Mouse Genome Database (MGD) Project, Gene Expression Database (GXD) Project, Mouse Tumor Biology (MTB) Database Project, Gene Ontology (GO) Project at MGI, and MouseCyc Project at MGI.
View all literature mentionsThis monoclonal targets β-Actin
View all literature mentionsThis monoclonal targets FLAG
View all literature mentionsThis monoclonal targets Chondroitin 4 Sulfate
View all literature mentionsThis polyclonal targets HA-probe
View all literature mentionsThis monoclonal targets casein kinase IIalpha
View all literature mentionsThis polyclonal targets Phosphoserine/threonine
View all literature mentionsThis polyclonal targets Ki67 antibody - Proliferation Marker
View all literature mentionsThis polyclonal targets CSGLCAT antibody
View all literature mentionsThis monoclonal targets Gsk3b
View all literature mentionsThis monoclonal targets Bad (D24A9) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-Bad (Ser136) (D25H8) Rabbit mAb
View all literature mentionsThis monoclonal targets PI3 Kinase p85
View all literature mentionsThis monoclonal targets PTEN, phospho (Ser380 / Thr382 / Thr383)
View all literature mentionsThis polyclonal targets p44/42 MAPK (Erk1/2)
View all literature mentionsThis polyclonal targets Erk1/2
View all literature mentionsThis monoclonal targets MEK1
View all literature mentionsThis monoclonal targets Phospho-MEK1/2 (Ser217/221)
View all literature mentionsThis monoclonal targets Phospho-Akt (Thr308) (C31E5E) Rabbit mAb
View all literature mentionsThis monoclonal targets Phospho-Akt (Ser473)
View all literature mentionsThis monoclonal targets Akt1
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Mus musculus with name NOD.Cg-Prkdcscid Il2rg
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