Transcription Regulation and Genome Rewiring Governing Sensitivity and Resistance to FOXM1 Inhibition in Breast Cancer.

ABSTRACT: Forkhead box M1 (FOXM1), an oncogenic transcription factor associated with aggressiveness and highly expressed in many cancers, is an emerging therapeutic target. Using novel 1,1-diarylethylene-diammonium small molecule FOXM1 inhibitors, we undertook transcriptomic, protein, and functional analyses to identify mechanisms by which these compounds impact breast cancer growth and survival, and the changes that occur in estrogen receptor (ERα)-positive and triple negative breast cancer cells that acquire resistance upon long-term treatment with the inhibitors. In sensitive cells, these compounds regulated FOXM1 gene networks controlling cell cycle progression, DNA damage repair, and apoptosis. Resistant cells showed transcriptional alterations that reversed the expression of many genes in the

SUBMITTER: Ziegler Y 

PROVIDER: S-EPMC8699539 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature