Modulatory effects of point‐mutated IL‐32θ (A94V) on tumor progression in triple‐negative breast cancer cells

Abstract Breast cancer is a frequently diagnosed cancer and the leading cause of death among women worldwide. Tumor‐associated macrophages stimulate cytokines and chemokines, which induce angiogenesis, metastasis, proliferation, and tumor‐infiltrating immune cells. Although interleukin‐32 (IL‐32) has been implicated in the development and modulation of several cancers, its function in breast cancer remains elusive. Mutation of interleukin‐32θ (IL‐32θ) in the tissues of patients with breast cancer was detected by Sanger sequencing. RT‐qPCR was used to detect the mRNA levels of inflammatory cytokines, chemokines, and mediators. The secreted proteins were detected using respective enzyme‐linked immunosorbent assays. Evaluation of the inhibitory effect of mutant IL‐32θ on proliferation, migration, epithelial–mesenchymal transition (EMT), and cell cycle arrest in breast cancer cells was conducted using MTS assays, migration assays, and Western blotting. A point mutation (281C>T, Ala94Val) was detected in IL‐32θ in both breast tumors and adjacent normal tissues, which suppressed the expression of pro‐inflammatory factors, EMT factors, and cell cycle related factors. Mutated IL‐32θ inhibited the expression of inflammatory factors by regulating the NF‐κB pathway. Furthermore, mutated IL‐32θ suppressed EMT markers and cell cycle related factors through the FAK/PI3K/AKT pathway. It was inferred that mutated IL‐32θ modulates breast cancer progression. Mutated IL‐32θ (A94V) inhibited inflammation, EMT, and proliferation in breast cancer by regulating the NF‐κB (p65/p50) and FAK‐PI3K‐GSK3 pathways.