CCNL1 Activates the NF-κB Pathway Through DVL3 Inhibition and PI3K/AKT Pathway Promotion in Breast Cancer.

Cyclin L1 (CCNL1) is highly expressed in multiple cancer types and has been linked to poor prognosis. However, the expression pattern of CCNL1 in breast cancer and its specific role in regulating breast cancer progression remain largely unknown. This study used cell and molecular biology techniques to examine how CCNL1 regulates the proliferation, invasion, migration, and epithelial-mesenchymal transition (EMT) of breast cancer cells. The applied methods encompassed plasmid transfection, Transwell assay, wound-healing assay, Western blot analysis, co-immunoprecipitation (Co-IP), and rescue assay. For the analysis of CCNL1-related factors and pathways, bioinformatics platforms including Metascape and HURI were also employed. CCNL1 is highly expressed in breast cancer cells and is associated with a poor prognosis. CCNL1 overexpression increased breast cancer cell invasion and migration and accelerated proliferation. Overexpression of CCNL1 was found to upregulate the mesenchymal marker Vimentin and downregulate the epithelial marker E-cadherin expression. There is close relationship between CCNL1, the NF-κB and PI3K/AKT signaling pathways. The direct interaction is verified between CCNL1 and DVL3 by Co-IP, indicating a negative correlation between the two proteins. CCNL1 overexpression affects breast cancer cells' paclitaxel sensitivity through the PI3K/AKT pathway. CCNL1 activates the NF-κB signaling pathway through its interaction with DVL3; additionally, it promotes the PI3K/AKT pathway. Together, these two mechanisms enable CCNL1 to exert a regulatory role in the progression of breast cancer.