PRL-3 promotes epithelial mesenchymal transition by regulating cadherin directly
PRL-3 promotes epithelial mesenchymal transition by regulating cadherin directly
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PRL-3通过直接调节钙粘蛋白促进上皮间质转化
DOI：
10.4161/cbt.8.14.8695
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发表时间：
2009-07-15
影响因子：
3.6
通讯作者：
Li, Jianming
中科院分区：
文献类型：
--
作者：
Liu, Yuhong;Zhou, Jun;Li, Jianming
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 down-regulating E-cadhrin 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-3 beta inactivated by PRL-3 as assessed by phosphospecific antibodies was a key event in EMT induced by PRL-3. Inhibition of glycogen synthase kinase-3 beta by lithium chloride, a highly selective inhibitor, leading to phosphorylation of glycogen synthase kinase-3 beta 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.
