The CNPY2 enhances epithelial-mesenchymal transition via activating the AKT/GSK3β pathway in non-small cell lung cancer.

The survival of non-small cell lung cancer (NSCLC) is poor due to high metastasis, and the indispensable step of metastasis includes epithelial-mesenchymal transition (EMT). In the study, by analyzing the dataset of the Cancer Genome Atlas (TCGA), we found that the expression of Canopy homolog 2 (CNPY2) is increased both in adenocarcinoma and squamous cell carcinoma, which is further confirmed in NSCLC tissues. Not only that, there is a negative correlation between CNPY2 and E-cadherin expression at mRNA level. Wound healing and transwell matrix penetration assay showed that overexpression of CNPY2 promotes the capability for invasion and metastasis of NSCLC cells. Further analysis uncovered that overexpression of CNPY2 can activate the AKT/GSK3β pathway, which leads to the inactivation of GSK-3β. The inactivation of GSK-3β increases the level of Snail, and then decreases the expression of E-cadherin to promote EMT. Eventually, inhibition of AKT suppresses the malignant transformation of CNPY2-upregulated cells. The above results suggest that CNPY2 may be served as a novel therapeutic target to therapy the NSCLC.