KLF9 inhibits breast cancer metastasis by up-regulating E-cadherin

Abstract

Abstract Krüppel-like factor 9 (KLF9) plays an inhibitory role in the process of breast cancer metastasis. The metastasis of tumor cells is often related to epithelial-mesenchymal transition (EMT). Among them, the gradual decrease of E-cadherin expression on cell surface is an important feature of EMT process. However, the concrete mechanism involved in this process remains largely unknown. In order to explore the mechanism, we have done relevant research. Through the analysis of transcriptome data in TCGA database and immunohistochemistry, we found that KLF9 was at a low expression level in breast cancer patients. The expression of KLF9 was positively correlated with the expression of E-cadherin in breast cancer cells. Functionally, KLF9 transcriptionally up-regulated E-cadherin expression and inhibited breast cancer metastasis, depending on its DBD domain. Mechanistically, KLF9 promoted E-cadherin promoter activity by binding to the CACCC motif (-12 to + 8), increasing the mRNA and protein level of E-cadherin. We also found that KLF9 can compete with SNAI1 to bind to the promoter region(-206 to + 47)of E-cadherin, and inhibit the transcriptional activity of SNAI1, leading to the activation of E-cadherin in breast cancer cells. Taken together, these results confirmed a new mechanism by which KLF9 could up-regulate E-cadherin expression to inhibit breast cancer metastasis, providing a research support for the prevention and treatment of breast cancer.