PRL-3 promotes epithelial mesenchymal transition by regulating cadherin directly
| Autor: | Yanqing Ding, Weizhe Gao, Yu-hong Liu, Jun Zhou, Yi Le, Jianming Li, Juanzhi Chen |
|---|---|
| Rok vydání: | 2009 |
| Předmět: |
endocrine system
Cancer Research Pathology medicine.medical_specialty Mice Nude Vimentin Adenocarcinoma Metastasis Mesoderm Cytokeratin Glycogen Synthase Kinase 3 Mice Cell Line Tumor Protein Interaction Mapping medicine Cell Adhesion Animals Humans Epithelial–mesenchymal transition Glycogen synthase Pharmacology Gene knockdown Glycogen Synthase Kinase 3 beta biology Cadherin Mesenchymal stem cell Epithelial Cells medicine.disease Cadherins Neoplasm Proteins Gene Expression Regulation Neoplastic Oncology Gene Knockdown Techniques Cell Transdifferentiation Colonic Neoplasms biology.protein Cancer research Molecular Medicine Snail Family Transcription Factors Protein Tyrosine Phosphatases Lithium Chloride hormones hormone substitutes and hormone antagonists Transcription Factors |
| Zdroj: | Cancer biologytherapy. 8(14) |
| ISSN: | 1555-8576 |
| Popis: | PRL-3 is a key gene associated with progression and metastasis of colorectal cancer. Recently PRL-3 was suggested to promote epithelial mesenchymal transition (EMT) by downregulating E-cadherin expression. But the mechanisms of EMT induced by PRL-3 remain largely unknown. Here we found that PRL-3 could also promote EMT in a colorectal cancer cell model SW480 with deficient E-cadherin expression in vivo and in vitro. PRL-3 stable overexpression or knockdown SW480 cells were injected subcutaneously into nude mice. Immunohistochemical analyses of tumor samples from nude mice showed that PRL-3 promoted upregulation of mesenchymal marker vimentin and downregulation of epithelial markers E-cadherin and cytokeratin. Glycogen synthase kinase-3beta inactivated by PRL-3 as assessed by phosphospecific antibodies was a key event in EMT induced by PRL-3. Inhibition of glycogen synthase kinase-3beta by lithium chloride, a highly selective inhibitor, leading to phosphorylation of glycogen synthase kinase-3beta increased Snail expression. In order to identify the direct effects of PRL-3, we isolated CDH22, one member of cadherin family, as a new candidate of interacting proteins of PRL-3 in yeast two-hybrid systems, and the interaction was confirmed in vitro by GST pull-down assay or in exogenous cell systems and endogenous colorectal cancer cells by co-immunoprecipitation assay and co-localization analysis. We observed that PRL-3 promoted downregulation of CDH22 expression. Interestingly, expression of E-cadherin was recovered in SW480 cells after PRL-3 was knocked-down. Our results first linked PRL-3 to cadherin directly. It provided new insights into the regulatory mechanisms of EMT induced by PRL-3. |
| Databáze: | OpenAIRE |
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