ORIGINAL ARTICLE

You have free access to this content

Epac1 promotes melanoma metastasis via modification of heparan sulfate

  1. Erdene Baljinnyam1,
  2. Masanari Umemura1,
  3. Mariana S. De Lorenzo1,
  4. Mizuka Iwatsubo1,
  5. Suzie Chen2,
  6. James S. Goydos3,
  7. Kousaku Iwatsubo1,4

Article first published online: 13 MAY 2011

DOI: 10.1111/j.1755-148X.2011.00863.x

Issue

Pigment Cell & Melanoma Research

Pigment Cell & Melanoma Research

Volume 24, Issue 4, pages 680–687, August 2011

Additional Information

How to Cite

Baljinnyam, E., Umemura, M., De Lorenzo, M. S., Iwatsubo, M., Chen, S., Goydos, J. S. and Iwatsubo, K. (2011), Epac1 promotes melanoma metastasis via modification of heparan sulfate. Pigment Cell & Melanoma Research, 24: 680–687. doi: 10.1111/j.1755-148X.2011.00863.x

Author Information

  1. 1

     Department of Cell Biology and Molecular Medicine, New Jersey Medical School-University of Medicine and Dentistry of New Jersey, Newark, NJ, USA

  2. 2

     Department of Chemical Biology, Susan Lehman Cullen Laboratory of Cancer Research in the Ernest Mario School of Pharmacy, Rutgers University, Piscataway, NJ, USA

  3. 3

     Division of Surgical Oncology, Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick, NJ, USA

  4. 4

     Cardiovascular Research Institute, Yokohama City University Graduate School of Medicine, Yokohama, Japan

*K. Iwatsubo, e-mail: iwatsuko@umdnj.edu

Publication History

  1. Issue published online: 18 AUG 2011
  2. Article first published online: 13 MAY 2011
  3. Accepted manuscript online: 19 APR 2011 09:37AM EST
  4. PUBLICATION DATA Received 18 September 2010, revised and accepted for publication 14 April 2011, published online 19 April 2011

SEARCH

SEARCH BY CITATION

ARTICLE TOOLS

View Full Article with Supporting Information (HTML) Get PDF (595K)

Keywords:

  • melanoma;
  • Epac;
  • heparan sulfate;
  • migration;
  • NDST-1;
  • tissue microarray;
  • N-sulfation

Summary

Our previous report suggested the potential role of the exchange protein directly activated by cyclic AMP (Epac) in melanoma metastasis via heparan sulfate (HS)-mediated cell migration. In order to obtain conclusive evidence that Epac1 plays a critical role in modification of HS and melanoma metastasis, we extensively investigated expression and function of Epac1 in human melanoma samples and cell lines. We have found that, in human melanoma tissue microarray, protein expression of Epac1 was higher in metastatic melanoma than in primary melanoma. In addition, expression of Epac1 positively correlated with that of N-sulfated HS, and N-deacetylase/N-sulfotransferase-1 (NDST-1), an enzyme that increases N-sulfation of HS. Further, an Epac agonist increased, but ablation of Epac1 decreased, expressions of NDST-1, N-sulfated HS, and cell migration in various melanoma cell lines. Finally, C8161 cells with stable knockdown of Epac1 showed a decrease in cell migration, and metastasis in mice. These data suggest that Epac1 plays a critical role in melanoma metastasis presumably because of modification of HS.

View Full Article with Supporting Information (HTML) Get PDF (595K)