Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers

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Abstract

The transcription factor KLF5 (Krüpple-like factor 5) is highly expressed in basal-like breast cancer (BLBC), which promotes cell proliferation, survival, migration and stemness, serving as a potential therapeutic target. In the current study, a super-enhancer (SE) was identified to be located downstream of the KLF5 gene in BLBC cell lines, HCC1806 and HCC1937. JQ-1, a BRD4 inhibitor, inhibits the expression and activity of KLF5 in both HCC1806 and HCC1937 cells in a time- and dose-dependent manner. Compound 870, an in-house BRD4 inhibitor, exhibited higher potency than JQ-1 to inhibit KLF5 and BLBC growth by arresting cells in G1 phase. Additionally, THZ1, a CDK7 inhibitor, also inhibits KLF5 and BLBC growth in a similar manner. Our findings suggested that KLF5 is regulated by SE, and modulation of SE could be an effective therapeutic strategy for treating BLBC.

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Chen, C. H., Yang, N., Zhang, Y., Ding, J., Zhang, W., Liu, R., … Chen, C. (2019). Inhibition of super enhancer downregulates the expression of KLF5 in basal-like breast cancers. International Journal of Biological Sciences, 15(8), 1733–1742. https://doi.org/10.7150/ijbs.35138

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