Krüppel-like factor 10 promotes the progression of breast cancer by activating canonical NF-κB signaling

The elevation of NF-κB activity is frequently found in more malignant cancer types; however, the cause of this activation has still been controversial. Here, we showed that KLF10 promoted breast cancer progression by activating the NF-κB cascade. Mechanistically, KLF10 transcriptionally upregulated <i>RELA</i> mRNA expression. ChIP assay further validated the binding of KLF10 to the <i>RELA</i> promoter. Additionally, by interacting with IκBα and promoting its proteasomal degradation, KLF10 facilitated the release and nuclear translocation of p65, thereby activating the NF-κB signaling. The phosphorylated p65 level was dramatically increased upon KLF10 overexpression. Several targets of NF-κB, including <i>TNF</i>, <i>VEGFA</i>, <i>PLAU</i>, <i>MMP9</i>, <i>ICAM1</i>, <i>CCND1</i>, and <i>MYC</i>, were also upregulated by KLF10. <i>In vivo</i> experiments confirmed that KLF10 promoted breast cancer metastasis, with its expression positively correlated with p65 and negatively correlated with IκBα. Overall, our study elucidates a previously unidentified mechanism driving breast cancer progression, wherein the NF-κB signaling is drastically activated.