The Dietary Supplement Chondroitin-4-Sulfate Exhibits Oncogene-Specific Pro-tumor Effects on BRAF V600E Melanoma Cells. Academic Article uri icon

Overview

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.

publication date

  • March 15, 2018

Research

keywords

  • Carcinogens
  • Cell Transformation, Neoplastic
  • Chondroitin Sulfates
  • Dietary Supplements
  • Melanoma
  • Mutation
  • Proto-Oncogene Proteins B-raf
  • Skin Neoplasms

Identity

PubMed Central ID

  • PMC5858191

Scopus Document Identifier

  • 85056210485

Digital Object Identifier (DOI)

  • 10.1016/j.molcel.2018.02.010

PubMed ID

  • 29547721

Additional Document Info

volume

  • 69

issue

  • 6