Wnt5a promotes epithelial-to-mesenchymal transition and metastasis in non-small-cell lung cancer.

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.

Wang B ，Tang Z ，Gong H ，Zhu L ，Liu X ... -  《-》

SOX9 drives the epithelial-mesenchymal transition in non-small-cell lung cancer through the Wnt/β-catenin pathway.

Huang JQ ，Wei FK ，Xu XL ，Ye SX ，Song JW ，Ding PK ，Zhu J ，Li HF ，Luo XP ，Gong H ，Su L ，Yang L ，Gong LY ... -  《Journal of Translational Medicine》

FOXP3 promotes tumor growth and metastasis by activating Wnt/β-catenin signaling pathway and EMT in non-small cell lung cancer.

Yang S ，Liu Y ，Li MY ，Ng CSH ，Yang SL ，Wang S ，Zou C ，Dong Y ，Du J ，Long X ，Liu LZ ，Wan IYP ，Mok T ，Underwood MJ ，Chen GG ... -  《Molecular Cancer》

Downregulation of miR-3127-5p promotes epithelial-mesenchymal transition via FZD4 regulation of Wnt/β-catenin signaling in non-small-cell lung cancer.

MiR-3127-5p has been implicated as a tumor-suppressive microRNA (miRNA) in non-small-cell lung cancer (NSCLC) and its expression was associated with tumor recurrence and poor prognosis. The aim of this study was to determine whether miR-3127-5p regulates epithelial-mesenchymal transition (EMT) in NSCLC, and to investigate the underlying mechanisms. Using qRT-PCR, we examined the expression levels of miR-3127-5p in a cohort of primary NSCLC specimens with and without distant metastasis. We further performed a series of in vitro and in vivo experiments to investigate the effects and underlying mechanism of miR-3127-5p on EMT, cell migration, invasion, and adhesion in NSCLC. We found that metastatic NSCLC tissues showed markedly downregulated miR-3127-5p expression. Transforming growth factor-β1 (TGF-β1) treatment induced EMT in A549 and H1299 cells, and downregulation of miR-3127-5p could result in the similar effect. Mechanically, we demonstrated that frizzled-4 (FZD4) is a target gene and miR-3127-5p exerts its effects by regulating the Wnt/β-catenin signaling. In addition, the expression levels of FZD4 and miR-3127-5p were also negatively associated in both clinical and xenografted tumors. Overall, these findings suggest that downregulation of miR-3127-5p promotes EMT through activating the Wnt/FZD4/β-catenin signaling pathway and may represent a therapeutic target for NSCLC metastasis.

Yang Y ，Sun Y ，Wu Y ，Tang D ，Ding X ，Xu W ，Su B ，Gao W ... -  《-》

MTA1 promotes epithelial to mesenchymal transition and metastasis in non-small-cell lung cancer.

Ma K ，Fan Y ，Dong X ，Dong D ，Guo Y ，Wei X ，Ning J ，Geng Q ，Wang C ，Hu Y ，Li M ，Niu W ，Li E ，Wu Y ... -  《Oncotarget》