BCL9 promotes epithelial mesenchymal transition and invasion in cisplatin resistant NSCLC cells via β-catenin pathway.

Bcell lymphoma 9 (BCL9)-Wnt/β-catenin pathway, a key signaling pathway related to epithelial-mesenchymal transition (EMT), is widely considered to be involved in invasion in various malignant tumors. However, the dysregulation of BCL9/β-catenin pathway in non-small cell lung cancer (NSCLC) has not been revealed. This study aimed to investigate the correlation between chemotherapy resistance and BCL9/Wnt/β-catenin signaling dysfunction. We performed BCL9 knockdown using a lentivirus-mediated sh-RNA interference in cisplatin-resistant (CR) lung cancer cells. Subsequently, the migration and invasion were determined by wound-healing and Transwell assays. Furthermore, EMT markers and β-catenin were examined by Western blot. Immunofluorescence was used to investigate the subcellular localization of β-catenin. The chemotherapeutic sensitivity to cisplatin in A549/DDP cell lines after treatment with BCL9 sh-RNA was estimated by MTT assay. The knockdown of BCL9 remarkably reduced the migration and invasion abilities of A549/DDP cells. Meanwhile, nuclear translocation of β-catenin was reduced after BCL9 was knocked down. BCL9 silencing also resulted in the downregulation of EMT-related proteins. Additionally, the Wnt/β-catenin agonist, CP21, significantly restored the expression of β-catenin and abilities of migration and invasion in BCL9-knockdown A549/DDP cell lines. Finally, we proved that the inhibition of BCL9 could partially attenuate the stemness of cancer cells and recover the chemotherapeutic sensitivity. These findings indicated BCL9 induced the occurrence of EMT and enhancement of stemness, which resulted in cisplatin-resistance and promoted migration in NSCLC cells. Mechanically, Wnt/β-catenin pathway is crucial in BCL9-induced migration, invasion, and chemotherapy resistance.

Zhang Y ，Zhang Q ，Chen H ，Wang C ... -  《-》

DKK1 promotes migration and invasion of non-small cell lung cancer via β-catenin signaling pathway.

Zhang J ，Zhang X ，Zhao X ，Jiang M ，Gu M ，Wang Z ，Yue W ... -  《-》

[Role of SOX4 on DDP Resistance in Non-small Cell Lung Cancer Cell of A549].

Li W ，Liu X ，Zhang G ，Zhang L ... -  《-》

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》

Mdig suppresses epithelial-mesenchymal transition and inhibits the invasion and metastasis of non‑small cell lung cancer via regulating GSK-3β/β-catenin signaling.

Geng F ，Jiang Z ，Song X ，Zhou H ，Zhao H ... -  《-》