Phosphatase of regenerating liver-3 inhibits invasiveness and proliferation in non-small cell lung cancer by regulating the epithelial-mesenchymal transition

Abstract

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/GSK3β/β-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.

Matrine inhibits the invasive and migratory properties of human hepatocellular carcinoma by regulating epithelial‑mesenchymal transition

“…Previous studies highlighted EMT as the mechanism by which differentiated epithelial cells undergo notable morphological alterations and acquire more motile and invasive capabilities ( 16 – 19 ). Cytoskeletal reorganization is also a characteristic of EMT and this feature was observed by F-actin staining.…”

Cathepsin L upregulation-induced EMT phenotype is associated with the acquisition of cisplatin or paclitaxel resistance in A549 cells

“…It illustrates a possible relationship between drug resistance and invasive potential, as further confirmed by our results. Accumulating evidence has highlighted EMT as the mechanism by which differentiated epithelial cells undergo remarkable morphological changes and acquire more motile and invasive capabilities [29][30][31][32] . Here, we found that A549/ DDP and A549/TAX cells were spindle-shaped and exhibited reduced cell contact ( Figure 3A).…”

P4HA3 is Epigenetically Activated by Slug in Gastric Cancer and its Deregulation is Associated With Enhanced Metastasis and Poor Survival

“…12,13 Slug, which is also known as SNAI2, is a transcription factor that is involved in regulation of ECM in GC. 14,15 In this study, we found that P4HA3 is significantly upregulated in GC than in normal tissues, and its upregulation is epigenetically activated by Slug. Also, we also observed that P4HA3 upregulation is associated with GC metastasis and poor survival.…”