Induction of the TEAD Co-activator VGLL1 by Estrogen Receptor-Targeted Therapy Drives Resistance in Breast Cancer.

ABSTRACT: Resistance to endocrine therapies (ET) is common in estrogen receptor (ER) positive breast cancer, and most relapsed patients die with ET-resistant disease. While genetic mutations provide explanations for some relapses, mechanisms of resistance remain undefined in many cases. Drug-induced epigenetic reprogramming has been shown to provide possible routes to resistance. By analyzing histone H3 lysine 27 acetylation (H3K27ac) profiles and transcriptional reprogramming in models of ET resistance, we discovered that selective ER degraders (SERDs), such as fulvestrant, promote expression of VGLL1, a co-activator for TEAD transcription factors. VGLL1, acting via TEADs, promoted expression of genes that drive growth of fulvestrant-resistant breast cancer cells. Pharmacological disruption of VGLL

SUBMITTER: Gemma C 

PROVIDER: S-EPMC7616691 | biostudies-literature | 2024 Oct

REPOSITORIES: biostudies-literature