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 |
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