Department of Radiology, The First Hospital of Lanzhou University, Lanzhou, Gansu, P.R. China.
The First Clinical Medical College of Lanzhou University, Lanzhou, Gansu, P.R. China.
Cell Biol Int. 2018 Aug;42(8):959-964. doi: 10.1002/cbin.10961. Epub 2018 Apr 17.
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.
由于高转移率，非小细胞肺癌（NSCLC）的存活率很差，而转移必不可少的步骤包括上皮-间充质转化（EMT）。在这项研究中，通过分析癌症基因组图谱（TCGA）的数据集，我们发现 Canopy 同源物 2（CNPY2）的表达在腺癌和鳞状细胞癌中均增加，这在 NSCLC 组织中得到了进一步证实。不仅如此，CNPY2 的表达与 mRNA 水平的 E-钙黏蛋白表达呈负相关。划痕愈合和 Transwell 基质渗透实验表明，CNPY2 的过表达促进了 NSCLC 细胞的侵袭和转移能力。进一步分析揭示，CNPY2 的过表达可以激活 AKT/GSK3β 途径，导致 GSK-3β 的失活。GSK-3β 的失活增加了 Snail 的水平，从而降低了 E-钙黏蛋白的表达，促进 EMT。最终，抑制 AKT 抑制了 CNPY2 上调细胞的恶性转化。上述结果表明，CNPY2 可能成为治疗 NSCLC 的新的治疗靶点。
