Abstract
A recent study indicated that high Wnt5a expression is associated with poor prognosis in non-small-cell lung cancer (NSCLC) patients; however, the underlying mechanism was not clear yet. Immunohistochemistry and Western blotting were performed to examine the protein expression level in NSCLC tissues and cell lines. The role of Wnt5a in clone formation, invasiveness, migration, and epithelial-to-mesenchymal transition (EMT) of NSCLC cells was studied. Luciferase reporter assay was used to evaluate the Tcf/Lef transcriptional activity. For assessing the effects of Wnt5a on tumor growth and metastasis in vivo, A549 cells transfected with sh-Wnt5a were subcutaneously or orthotopically injected into nude mice. In NSCLC tissues, higher expression levels of Wnt5a and ROR2 were found, β-Catenin was expressed exceptionally, and EMT was prompted. Wnt5a overexpression increased clone formation, migration, and invasion, as well as prompted EMT of NSCLC cell in vitro, whereas Wnt5a knockdown showed the absolutely reversed results. Wnt5a overexpression enhanced the Tcf/Lef transcriptional activity and elevated the nuclear β-catenin level in NSCLC cells, without altering the ROR2 expression. We also demonstrated that si-β-catenin antagonized Wnt5a overexpression nduced EMT and invasiveness. Besides, in vivo experiment showed that sh-Wnt5a significantly increased tumor volume and tumor weight, and prompted EMT in A549 tumor-bearing mice as compared with the control. No metastasis was found in the liver tissue after sh-Wnt5a-transfected cells were orthotopically injected into nude mice as compared with the control. In conclusion, Wnt5a promotes EMT and metastasis in NSCLC, which is involved in the activation of β-catenin-dependent canonical Wnt signaling.
Highlights
Lung cancer, which is classified into small cell lung cancer, squamous cell carcinoma (SCC), adenocarcinoma (ADC), and large cell carcinoma, remains the leading cause of cancer deaths in the world
We examined Wnt family member 5A (Wnt5a), receptor tyrosine kinase like orphan receptor 2 (ROR2), and β-Catenin expression in non-small-cell lung cancer (NSCLC) tissues (ADC and SCC) and matched adjacent normal lung tissues by the immunohistochemistry analysis
We detected the expression of Wnt5a and epithelial-to-mesenchymal transition (EMT)-related proteins E-cadherin, N-cadherin, and vimentin in NSCLC tissues; the results (Figure 1B) showed that the expression of Wnt5a was higher in NSCLC tissues than that in adjacent normal lung tissues, which is consistent with the immunohistochemistry analysis
Summary
Lung cancer, which is classified into small cell lung cancer, squamous cell carcinoma (SCC), adenocarcinoma (ADC), and large cell carcinoma, remains the leading cause of cancer deaths in the world. The latter three are included in the non-small-cell lung cancer (NSCLC) classification, and ADC and SCC are known to be the most important subtypes of NSCLC [1]. NSCLC accounts for nearly 80% of lung cancer cases [2]. EMT epithelial cells undergo morphological changes c 2017 The Author(s).
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