INVESTIGATING THE ROLE OF THE CHOLESTEROL TRANSPORTER, STARD3 IN ESTROGEN RECEPTOR-POSITIVE BREAST CANCER CELLS

Abstract

Breast cancer cells rely on tightly regulated cholesterol trafficking and growth factor signaling to support proliferation and migration. STARD3 is an endosomal cholesterol transfer protein frequently co-amplified with HER2, yet its biological role in estrogen-receptor positive (ER+) breast cancer remains unclear. Here, we investigated how STARD3 depletion affects proliferation, migration, and signaling in ER+ MCF-7 cells. Using a microRNA-based shRNA knockdown system, STARD3 expression was reduced at both the mRNA and protein levels. STARD3 depletion enhanced proliferation, increased CDK1 and GINS2 expression, and reduced the proportion of Ki67-negative (G0) cells. This proliferative advantage was not maintained when exogenous cholesterol availability was limited, indicating partial dependence. Despite enhanced proliferation, STARD3-depleted cells exhibited impaired wound-closure migration, suggesting a proliferation-migration trade-off. Elevated basal phosphorylation of focal adhesion kinase (FAK, Y397) implicates altered adhesion signaling. Together, these findings suggest that STARD3 maintains endosomal cholesterol homeostasis that supports adhesion-linked signaling in ER+ breast cancer cells.