Abstract 243P
Background
Tumor-associated macrophages (TAM) influence lung tumor development, and the β-catenin/FOSL2/ARID5A signaling pathway may be a key pathway regulating macrophage polarization, but the role of FOXP4 in regulating TAM polarization through the β-catenin/FOSL2/ARID5A signaling pathway in influencing the proliferation and invasion of lung cancer cells is unclear.
Methods
TAM was transfected with a plasmid knocking down FOXP4, co-cultured with lung cancer cells A549, and lung cancer nude mice with low expression of FOXP4 were prepared, and β-catenin agonist (SKL2001) or macrophage accumulation inhibitor (Ki20227) intervened in TAM or nude mice. M1/M2 phenotype, cell proliferation, migration, invasion, β-catenin/FOSL2/ARID5A pathway and histopathological changes were evaluated by flow cytometry, CCK-8, clone formation assay, scratch assay, Transwell, qRT-PCR, Western blot and HE staining.
Results
FOXP4 was highly expressed in TAM, and FOXP4 interacted with β-catenin proteins, and low expression of FOXP4 inhibited the proliferation, invasion, and migration of lung cancer, and enhanced the polarization of TAM to M1-type macrophages, and affected the transcription of the β-catenin/FOSL2/ARID5 signaling pathway. Moreover, in vivo silencing of FOXP4 regulated TAM polarization and promoted apoptosis in lung cancer.
Conclusions
The results demonstrate that FOXP4 promotes lung cancer cell proliferation and invasion by regulating TAM polarization through the β-catenin/FOSL2/ARID5A signaling pathway.
Legal entity responsible for the study
The authors.
Funding
Has not received any funding.
Disclosure
All authors have declared no conflicts of interest.