Loading...
Conserved role of FOXC1 in TNBC is parallel to FOXA1 in ER+ breast cancer
Ramachandran, R. Ibragimova, S. Woods, L. M. AlHouqani, T. Gomez, R. L. Simeoni, Fabrizio Hachim, M. Y. Somervaille, T. C. P. Philpott, A. Carroll, J. S.
Ramachandran, R.
Ibragimova, S.
Woods, L. M.
AlHouqani, T.
Gomez, R. L.
Simeoni, Fabrizio
Hachim, M. Y.
Somervaille, T. C. P.
Philpott, A.
Carroll, J. S.
Citations
Altmetric:
Abstract
Triple-negative breast cancer (TNBC) is characterized by lack of the estrogen (ER) receptor, progesterone receptor (PR), and human epidermal growth factor receptor-2 (HER2), and standard receptor-targeted therapies are ineffective. FOXC1, a transcription factor aberrantly overexpressed in many cancers, drives growth, metastasis, and stem-cell-like properties in TNBC. However, the molecular function of FOXC1 is unknown, partly due to heterogeneity of TNBC. Here, we show that although FOXC1 regulates many cancer hallmarks in TNBC, its function is varied in different cell lines, highlighted by the differential response to CDK4/6 inhibitors upon FOXC1 loss. Despite this functional heterogeneity, we show that FOXC1 regulates key oncogenes and tumor suppressors and identify a set of core FOXC1 peaks conserved across TNBC cell lines. We identify the ER-associated and drug-targetable nuclear receptor NR2F2 as a cofactor of FOXC1. Finally, we show that core FOXC1 targets in TNBC are regulated in parallel by the pioneer factor FOXA1 and the nuclear receptor NR2F2 in ER + breast cancer.
Description
Date
2024
Publisher
Collections
Files
Keywords
Type
Article
Citation
Ramachandran R, Ibragimova S, Woods LM, AlHouqani T, Gomez RL, Simeoni F, et al. Conserved role of FOXC1 in TNBC is parallel to FOXA1 in ER+ breast cancer. iScience. 2024 Aug 16;27(8):110500. PubMed PMID: 39171293. Pubmed Central PMCID: PMC11338131. Epub 2024/08/22. eng.