Pleomorphic adenoma gene like-2 induces epithelial-mesenchymal transition via Wnt/β-catenin signaling pathway in human colorectal adenocarcinoma.

Abstract

Epithelial-mesenchymal transition (EMT) is a critical step in the acquisition of metastatic and invasive power for tumor cells. Colorectal adenocarcinoma (CRC) is a common cancer where metastasis is directly linked to patient survival. Recent studies show that pleomorphic adenoma gene like-2 (PLAGL2) could induce tumor EMT and is an independent predictive factor associated with poor prognosis in cancer. In the present study, we confirmed the role of PLAGL2 in the prognosis of CRC patients and provide molecular evidence of PLAGL2 promoted EMT in CRC cell line SW480. We found that PLAGL2 expression was upregulated in the paraffin-embedded CRC tissues compared to borderline or benign tissues. Experimental EMT induced by PLAGL2 plasmid transfection proved PLAGL2 protein overexpression could enhance the cell scratch wound-healing and Transwell ability and significantly upregulated mesenchymal marker proteins, N-cadherin and vimentin and concurrently downregulated epithelial marker of E-cadherin. Subsequently, through western blot assay, we found that PLAGL2 could activate the Wnt-signaling component β-catenin in the nuclei. More CRC cell metastasis to the lungs was observed when the PLAGL2 overexpressing SW480 cells were injected into the tail vein of rats, compared with the cell control and PLAGL2 silence group. Our findings indicated that PLAGL2 might be a very upstream key molecule regulating EMT involved in Wnt/β-catenin signaling pathway.