Phosphatase of regenerating liver-3 promotes motility and metastasis of mouse melanoma cells.
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.
Wu
Xiaopeng
X
State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, and the Model Animal Genetics Research Center, Nanjing University, Nanjing, China.
Zeng
Hu
H
Zhang
Xianming
X
Zhao
Ying
Y
Sha
Haibo
H
Ge
Xiaomei
X
Zhang
Minyue
M
Gao
Xiang
X
Xu
Qiang
Q
D000818:Animals; D001483:Base Sequence; D002455:Cell Division; D002465:Cell Movement / Q000502:physiology*; D003001:Cloning, Molecular; D017931:DNA Primers; D018076:DNA, Complementary; D006801:Humans; D017874:Immediate-Early Proteins / Q000235:genetics / Q000378:metabolism*; D007700:Kinetics; D008099:Liver / Q000201:enzymology*; D008113:Liver Neoplasms / Q000201:enzymology / Q000473:pathology; D008546:Melanoma, Experimental / Q000473:pathology* / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis / Q000473:pathology*; D009363:Neoplasm Proteins; D010744:Phosphoric Monoester Hydrolases / Q000235:genetics / Q000378:metabolism*; D017027:Protein Tyrosine Phosphatases / Q000235:genetics / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D017931:DNA Primers; D018076:DNA, Complementary; D017874:Immediate-Early Proteins; D009363:Neoplasm Proteins; C111534:Ptp4a3 protein, mouse; D011994:Recombinant Proteins; D010744:Phosphoric Monoester Hydrolases; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases