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

## TL;DR

This study shows that KLF10 promotes breast cancer by activating the NF-κB signaling pathway, leading to cancer cell growth and spread.

## Contribution

The paper reveals a new mechanism where KLF10 activates NF-κB by upregulating RELA and degrading IκBα.

## Key findings

- KLF10 promotes breast cancer proliferation and metastasis.
- KLF10 activates NF-κB by increasing RELA expression and degrading IκBα.
- NF-κB targets like TNF, VEGFA, and MMP9 are upregulated by KLF10.

## Abstract

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 RELA mRNA expression. ChIP assay further validated the binding of KLF10 to the RELA 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 TNF, VEGFA, PLAU, MMP9, ICAM1, CCND1, and MYC, were also upregulated by KLF10. In vivo 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.

•KLF10 promotes the proliferation and metastasis of breast cancer cells•NF-κB signaling is involved in KLF10-mediated cancer progression•KLF10 activates NF-κB by inducing RELA transcription and IκBα protein degradation

KLF10 promotes the proliferation and metastasis of breast cancer cells

NF-κB signaling is involved in KLF10-mediated cancer progression

KLF10 activates NF-κB by inducing RELA transcription and IκBα protein degradation

Biological sciences; Cancer