Phosphatase of regenerating liver 3 inhibits invasiveness and proliferation in non small cell lung cancer by regulating the epithelial mesenchymal transition
Phosphatase of regenerating liver 3 (PRL 3) has been reported to be associated with colon and gastric cancer metastasis. However, the role and function of PRL 3 in human non small cell lung cancer cells is unknown. Our studies showed that the expression of PRL 3mRNA and protein are higher in less invasive human lung adenocarcinoma cells than in highly invasive cell lines. Ectopic expression of PRL 3 reduced cell capacity for anchorage dependent growth, anchorage independent growth, migration, and invasion in vitro, as well as tumorigenesis in vivo. Conversely, catalytic (C104S) and prenylation site (C170S) mutants enhanced cell invasion. Microarray profiling of PRL 3 transfectants revealed the pathways potentially involving PRL 3, including the epithelial mesenchymal transition (EMT) extracellular matrix remodeling, and the WNT signaling pathway. Furthermore, we demonstrated that increased PRL 3 reduced Slug and enhanced E cadherin gene expression through the AKT/GSK3b/b catenin pathway. In conclusion, our data suggest that PRL 3 might play a tumor suppressor role in lung cancer, distinct from other cancers, by inhibiting EMT related pathways.
Oncotarget