Research Papers:

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

Sheng‑Yi Lin, Yue‑Xun Lee, Sung‑Liang Yu, Gee‑Chen Chang and Jeremy J.W. Chen _

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Oncotarget. 2016; 7:21799-21811. https://doi.org/10.18632/oncotarget.7985

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Sheng-Yi Lin1,2, Yue-Xun Lee1, Sung-Liang Yu3, Gee-Chen Chang1,4,*, Jeremy J.W. Chen1,2,*

1Institute of Biomedical Sciences, National Chung Hsing University, Taichung, Taiwan

2Agricultural Biotechnology Center, National Chung Hsing University, Taichung, Taiwan

3Department of Clinical Laboratory Sciences and Medical Biotechnology, National Taiwan University College of Medicine, Taipei, Taiwan

4Division of Chest Medicine, Department of Internal Medicine, Taichung Veterans General Hospital, Taichung, Taiwan

*These authors have contributed equally to this work

Correspondence to:

Jeremy J.W. Chen, e-mail: [email protected]

Keywords: PRL-3, NSCLC, invasion, migration, tumor growth

Received: August 20, 2015     Accepted: February 16, 2016     Published: March 08, 2016


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.

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