Journal
PLOS ONE
Volume 4, Issue 2, Pages -Publisher
PUBLIC LIBRARY SCIENCE
DOI: 10.1371/journal.pone.0004450
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Funding
- National Natural Science Foundation of China [30500619]
- Natural Science Foundation of Jiangsu Province, China [BK2007716, BK2008022]
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Background: Phosphatase of regenerating liver-3 (PRL-3) is a member of the novel phosphatases of regenerating liver family, characterized by one protein tyrosine phosphatase active domain and a C-terminal prenylation (CCVM) motif. Though widely proposed to facilitate metastasis in many cancer types, PRL-3's cellular localization and the function of its CCVM motif in metastatic process remain unknown. Methodology/Principal Findings: In the present study, a series of Myc tagged PRL-3 wild type or mutant plasmids were expressed in B16F1 melanoma cells to investigate the relationship between PRL-3's cellular localization and metastasis. With immuno-fluorescence microcopy and cell adhesion/migration assay in vitro, and an experimental passive metastasis model in vivo, we found that CCVM motif is critical for the localization of PRL-3 on cell plasma membrane and the lung metastasis of melanoma. In particular, Cystine 170 is the key site for prenylation in this process. Conclusions/Significance: These results suggest that cellular localization of PRL-3 is highly correlated with its function in tumor metastasis, and inhibition of PRL-3 prenylation might be a new approach to cancer therapy.
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