The dietary supplement chondroitin-4-sulfate exhibits oncogene-specific pro-tumor effects on BRAF V600E melanoma cells Journal Article


Authors: Lin, R.; Xia, S.; Shan, C.; Chen, D.; Liu, Y.; Gao, X.; Wang, M.; Kang, H. B.; Pan, Y.; Liu, S.; Chung, Y. R.; Abdel-Wahab, O.; Merghoub, T.; Rossi, M.; Kudchadkar, R. R.; Lawson, D. H.; Khuri, F. R.; Lonial, S.; Chen, J.
Article Title: The dietary supplement chondroitin-4-sulfate exhibits oncogene-specific pro-tumor effects on BRAF V600E melanoma cells
Abstract: 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. The pathogenic links between dietary supplements and oncogenic mutations remain unknown. In this article, Lin et al. demonstrate that chondroitin-4-sulfate, a dietary supplement widely used for osteoarthritis, selectively promotes BRAF-V600E melanoma growth and confers resistance to BRAF inhibitors, suggesting that the generally “safe” dietary supplements may exhibit oncogene-specific pro-tumor effects. © 2018 Elsevier Inc.
Keywords: melanoma; diet; dietary supplement; chondroitin sulfate; braf-v600e; csglca-t
Journal Title: Molecular Cell
Volume: 69
Issue: 6
ISSN: 1097-2765
Publisher: Cell Press  
Date Published: 2018-03-15
Start Page: 923
End Page: 937.e8
Language: English
DOI: 10.1016/j.molcel.2018.02.010
PROVIDER: scopus
PMCID: PMC5858191
PUBMED: 29547721
DOI/URL:
Notes: Article -- Export Date: 3 December 2018 -- Source: Scopus
Altmetric Score
MSK Authors
  1. Taha Merghoub
    209 Merghoub
  2. Young Rock Chung
    46 Chung