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PRL-3 and PRL-1 Promote Cell Migration, Invasion, and Metastasis^{1 ,2}

Institute of Molecular and Cell Biology, Singapore 117609, Singapore [Q. Z., J-M. D., K. G., J. L., H-X. T., V. K., E. M., W. H.]; Department of Pediatrics, University of British Columbia, BC Research Institute for Children’s and Women’s Health, Vancouver, British Columbia V5Z 4H4, Canada [C. J. P.]

We demonstrate here that Chinese hamster ovary cells stably expressing PRL-3, a M_r 20,000 prenylated protein tyrosine phosphatase, or its relative, PRL-1, exhibit enhanced motility and invasive activity. A catalytically inactive PRL-3 mutant has significantly reduced migration-promoting activity. We observe that PRL-3 is associated with diverse membrane structures involved in cell movement. Furthermore, we show that PRL-3- and -1-expressing cells, but not control cells, induce metastatic tumor formation in mice. Thus, our results deliver the first evidence for a causative role of PRL-3 and -1 in promoting cell motility, invasion activity, and metastasis.

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