Work

8523 An Unconventional Estrogen Receptor Conformation Induces SUMO Expression in Breast Cancer Cells

Year: 2024

Type: article

Abstract: Disclosure: G.R. Hancock: None. K. Young: None. G.L. Greene: None. S.W. Fanning: None. Competitive allosteric regulators, selective estrogen receptor modulators (SERMs)/degraders (SERDs) differentially manipulate receptor structure to treat and prevent metastatic breast cancers. However, their utility is limited by the ∼40% rate of disease progression due to acquired therapy resistance. In this study, a new SERM based on a tetrahydro-6-isoquinoline (T6I) scaffold reveals the relationship between ERα conformation and therapeutic transcriptional pathways in drug-resistant breast cancers. Optimization of structure-activity relationships produced unique lead compound that engages transcriptional programs similar to the clinically approved SERD fulvestrant. Notably, both drugs induce the expression of small ubiquitin-like modifier-1 (SUMO1), in opposition to the pathogenic hormone 17β-estradiol. SUMOylation is a post-translational modification affecting protein-protein interactions, localization, stability and functional properties. High expression of SUMO1 is associated with better patient prognosis in ERα+ disease. SUMOylation in breast cancer will be elucidated through understanding how it’s induced, its structural basis, and its role in therapeutic response of antiestrogen treatments. Presentation: 6/3/2024

Source: Journal of the Endocrine Society

DOI: 10.1210/jendso/bvae163.2222

Authors: Govinda R Hancock, Kristen Young, Geoffrey L Greene, Sean William Fanning

Institutions: Loyola University Chicago, University of Chicago

Language: English

Topic: Estrogen and related hormone effects

Subfield: Genetics

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,418