Inhibition of CXCR4 regulates epithelial mesenchymal transition of NSCLC via the Hippo-YAP signaling pathway.

CXCR4 has been shown to play a key role in the metastasis of non-small cell lung cancer (NSCLC). And CXCR may be associated with the Hippo-Yes kinase-associated protein (YAP) pathway, thus involving in the occurrence and progression of NSCLC. This study aims to investigate the effect of CXCR4 inhibition on epithelial-mesenchymal transition (EMT), invasion and migration of NSCLC cells via the Hippo-YAP pathway. QRT-PCR and Western blot were employed to detect CXCR4 expression in NSCLC cell lines. A549 and H1299 cells were treated with WZ811 (0, 10, 30, and 50 µM), and A549 cells were also divided into the Control, WZ811, YAP siRNA, and WZ811 + YAP groups. Wound-healing, Transwell assay, immunofluorescent staining, and a luciferase reporter gene assay were performed in this experiment. Compared with human bronchial epithelial (HBE) cells, CXCR4 expression was up-regulated in NSCLC cell lines. WZ811 increased E-cadherin; decreased expression of Twist, vimentin, Snail, p-YAP, CTGF, and BIRC5; blocked GTIIC reporter activity; and reduced migration and invasion of A549 cells, all in a dose-dependent manner. YAP siRNA had a similar effect to WZ811 by inhibiting EMT, invasion and migration of A549 cells. However, compared with A549 cells in the YAP siRNA and WZ811 groups, cells in the WZ811 + YAP group showed a dramatically enhanced EMT phenotype as well as invasion and migration abilities. Inhibition of CXCR4 may reduce EMT, invasion and migration of NSCLC cells, thereby providing a new therapeutic target for NSCLC.

Zheng CH ，Chen XM ，Zhang FB ，Zhao C ，Tu SS ... -  《-》

Twist may be associated with invasion and metastasis of hypoxic NSCLC cells.

Wei L ，Sun JJ ，Cui YC ，Jiang SL ，Wang XW ，Lv LY ，Xie L ，Song XR ... -  《-》

Inhibition of ERK1/2 down-regulates the Hippo/YAP signaling pathway in human NSCLC cells.

You B ，Yang YL ，Xu Z ，Dai Y ，Liu S ，Mao JH ，Tetsu O ，Li H ，Jablons DM ，You L ... -  《Oncotarget》

Metformin-repressed miR-381-YAP-snail axis activity disrupts NSCLC growth and metastasis.

Jin D ，Guo J ，Wu Y ，Chen W ，Du J ，Yang L ，Wang X ，Gong K ，Dai J ，Miao S ，Li X ，Su G ... -  《JOURNAL OF EXPERIMENTAL & CLINICAL CANCER RESEARCH》

Irisin suppresses the migration, proliferation, and invasion of lung cancer cells via inhibition of epithelial-to-mesenchymal transition.

Irisin is involved in promoting metabolism, immune regulation, and affects chronic inflammation in many systemic diseases, including gastric cancer. However, the role of irisin in lung cancer is not well characterized. To determine whether irisin has a protective effect against lung cancer, we cultured A549 and NCI-H446 lung cancer cells and treated them with irisin. We detected the proliferation by MTT assay, and assessed the migration and invasion of the cells by scratch wound healing assay and Tran-swell assay. The expression levels of epithelial-to-mesenchymal transition (EMT) markers and the related signaling pathways were detected by western blot analysis. Meanwhile, an inhibitor of PI3K was used to investigate the effect of irsin. Finally, the expression of Snail was detected. We demonstrated that irisin inhibits the proliferation, migration, and invasion of lung cancer cells, and has a novel role in mediating the PI3K/AKT pathway in the cells. Irisin can reverse the activity of EMT and inhibit the expression of Snail via mediating the PI3K/AKT pathway, which is a key regulator of Snail. These results revealed that irisin inhibited EMT and reduced the invasion of lung cancer cells via the PI3K/AKT/Snail pathway.

Shao L ，Li H ，Chen J ，Song H ，Zhang Y ，Wu F ，Wang W ，Zhang W ，Wang F ，Li H ，Tang D ... -  《-》