Kruppel-like factor 9 upregulates E-cadherin transcription and represses breast cancer invasion and metastasis

xlomafota13 shared this article with you from Inoreader Kruppel-like factor 9 upregulates E-cadherin transcription and represses breast cancer invasion and metastasis Via American Journal of Cancer Research Am J Cancer Res. 2021 Jul 15;11(7):3660-3673. eCollection 2021. ABSTRACT Aberrant expression of Krüppel-like factor 9 (KLF9) is frequently found in some types of cancer and is implicated in cancer initiation and progression. However, the effects of KLF9 on cancer metastases and the underlying mechanisms still need to be understood. Here, we found that KLF9 evidently inhibited the capabilities of migration and invasion of breast cancer cells. The expression of KLF9 was markedly decreased in breast cancer patients compared with benign tumors, and was positively correlated with the expression of E-cadherin in the tissues of breast cancer patients. Mechanistically, chromatin immunoprecipitation combined with site-directed mutagenesis-luciferase assay revealed that KLF9 activated the E-cadherin promoter by binding to GT-box elements located +84 bp and -143 bp from the TSS in the E-cadherin promoter, leading to elevated expression of E-cadherin mRNA and protein. In vivo experiments confirmed that KLF9 strongly inhibited the lung metastasis of breast cancer and increased mouse E-cadherin expression in 4T1 mouse breast cancer cells. Taken together, our findings demonstrated that KLF9 could suppress breast cancer invasion and metastasis by upregulating E-cadherin, which provided new insight into aggressive treatment of breast cancer by targeting the KLF9/E-cadherin axis. PMID:34354866 | PMC:PMC8332869 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.