Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells

Xiaopeng Wu, Hu Zeng, Xianming Zhang, Ying Zhao, Haibo Sha, Xiaomei Ge, Minyue Zhang, Xiang Gao, Qiang Xu

Research output: Contribution to journalArticlepeer-review

134 Scopus citations

Abstract

Recent reports suggested that phosphatase of regenerating liver (PRL)-3 might be involved in colorectal carcinoma metastasis with an unknown mechanism. Here we demonstrated that PRL-3 expression was up-regulated in human liver carcinoma compared with normal liver. PRL-3 was also highly expressed in metastatic melanoma B16-BL6 cells but not in its lowly metastatic parental cell line, B16 cells. B16 cells transfected with PRL-3 cDNA displayed morphological transformation from epithelial-like shape to fibroblast-like shape. PRL-3-overexpressed cells showed much higher migratory ability, which could be reversed by specific anti-sense oligodeoxynucleotide and the phosphatase inhibitors sodium orthovanadate or potassium bisperoxo oxovanadate V. Meanwhile, the expression of the catalytically inactive PRL-3 mutations (D72A or C104S) significantly reduced the cell migratory capability. In addition, PRL-3 transfectants demonstrated altered extracellular matrix adhesive property and up-regulated integrin-mediated cell spreading efficiency. Furthermore, we confirmed that PRL-3 could facilitate lung and liver metastasis of B16 cells in an experimental metastasis model in mice, consistent with accelerated proliferation and growth rate both in vitro and in vivo. Together, these observations provide convincing evidence that PRL-3 truly plays a causal role in tumor metastasis.

Original languageEnglish (US)
Pages (from-to)2039-2054
Number of pages16
JournalAmerican Journal of Pathology
Volume164
Issue number6
DOIs
StatePublished - Jun 2004

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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