Liver X receptors induce antiproliferative effects in basal‐like breast cancer

Abstract

Liver X receptors (LXRs) are nuclear transcription factors important in the regulation of cholesterol transport, and glucose and fatty acid metabolism. The antiproliferative role of LXRs has been studied in a variety of malignancies and may represent a therapeutic opportunity in cancers lacking targeted therapies, such as triple‐negative breast cancer. In this study, we investigated the impact of LXR agonists alone and in combination with carboplatin in preclinical models of breast cancer. In vitro experiments revealed a dose‐dependent decrease in tumor cell proliferation in estrogen receptor‐positive breast cancer cells, whereas LXR activation in vivo resulted in an increased growth inhibitory effect in a basal‐like breast cancer model (in combination with carboplatin). Functional proteomic analysis identified differences in protein expression between responding and nonresponding models related to Akt activity, cell‐cycle progression, and DNA repair. Furthermore, pathway analysis suggested that the LXR agonist in combination with carboplatin inhibits the activity of targets of E2F transcription factors and affects cholesterol homeostasis in basal‐like breast cancer.

Reprogramming of Lipid Metabolism Mediates Crosstalk, Remodeling, and Intervention of Microenvironment Components in Breast Cancer

“…Consequently, cholesterol metabolism may exhibit significant variations among different molecular subtypes of BC. The liver X receptor (LXR), a pivotal transcription factor involved in this process, effectively inhibits proliferation in ER+ and basal-like BC cells 65 . Activation of LXR by its ligand T0901317 suppresses the expression of Flotillin-2, a biomarker associated with lipid rafts 66 .…”