Epac1 promotes melanoma metastasis via modification of heparan sulfate.

Abstract

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.

• Authors: Erdene Baljinnyam, Masanari Umemura, Mariana S De Lorenzo, Mizuka Iwatsubo, Suzie Chen, James S Goydos, Kousaku Iwatsubo
• Journal: Pigment cell & melanoma research (Pigment Cell Melanoma Res) Vol. 24 Issue 4 Pg. 680-7 (Aug 2011) ISSN: 1755-148X [Electronic] England
• PMID: 21539721 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2011 John Wiley & Sons A/S.

Chemical References

• Guanine Nucleotide Exchange Factors
• RAPGEF3 protein, human
• RAPGEF4 protein, human
• Heparitin Sulfate
• Sulfotransferases
• heparitin sulfotransferase

Topics

• Animals
• Cell Line, Tumor
• Cell Movement
• Gene Deletion
• Guanine Nucleotide Exchange Factors (metabolism)
• Heparitin Sulfate (metabolism)
• Humans
• Melanoma (enzymology, metabolism, pathology)
• Mice
• Neoplasm Metastasis
• Skin Neoplasms (metabolism, pathology)
• Staining and Labeling
• Sulfotransferases (metabolism)