title: 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.
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.|Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Sheng-Yi
authors.initials: SY
authors.lastname: Lin
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Yue-Xun
authors.initials: YX
authors.lastname: Lee
authors.affiliation: Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Sung-Liang
authors.initials: SL
authors.lastname: Yu
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.|Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan.
authors.forename: Gee-Chen
authors.initials: GC
authors.lastname: Chang
authors.affiliation: Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan.|Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan.
authors.forename: Jeremy J W
authors.initials: JJ
authors.lastname: Chen
mesh_terms: D000072283:A549 Cells; D000818:Animals; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D020869:Gene Expression Profiling / Q000379:methods; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D053208:Kaplan-Meier Estimate; D008175:Lung Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D008819:Mice, Nude; D009154:Mutation; D009361:Neoplasm Invasiveness; D009363:Neoplasm Proteins / Q000235:genetics* / Q000378:metabolism; D017027:Protein Tyrosine Phosphatases / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction / Q000235:genetics; D014183:Transplantation, Heterologous
chemical_list: D015820:Cadherins; D009363:Neoplasm Proteins; C484730:PTP4A3 protein, human; D017027:Protein Tyrosine Phosphatases
keywords: NSCLC; PRL-3; invasion; migration; tumor growth