Phosphatase of regenerating liver-3 localizes to cyto-membrane and is required for B16F1 melanoma cell metastasis in vitro and in vivo.

• Main Authors: Ran Song, Feng Qian, Yu-Pei Li, Xia Sheng, Shao-Xian Cao, Qiang Xu
• Format: Article
• Language: English
• Published: Public Library of Science (PLoS) 2009-01-01
• Series: PLoS ONE
• Online Access: http://europepmc.org/articles/PMC2635958?pdf=render

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, Cystine170 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.