Abstract 6646: Fibroblast growth factor receptor signaling modulates cholesterol storage in a SOAT1-dependent manner to promote mammary tumor cell invasion

Abstract Signaling by fibroblast growth factor receptors (FGFRs) is active in up to 85% of breast cancers and results in enhanced proliferation, migration, and invasion of tumor cells. Here, we show that FGFR signaling regulates cholesterol metabolism in breast cancer. Specifically, we demonstrate that FGFR activation promotes cellular cholesterol storage by upregulating expression of the enzyme sterol O-acyltransferase 1 (SOAT1). Moreover, we demonstrate that inhibition of SOAT1 attenuates FGFR-driven colony formation and invasion in tumor cells. Finally, we identify a relationship between SOAT1 inhibition and decreased expression of matrix metalloproteinases by tumor cells. Taken together, these findings suggest a previously undiscovered metabolic role for FGFR signaling in breast cancer and present a therapeutic vulnerability that could be targeted in FGFR-driven cancers. Citation Format: Jennifer E. Tuokkola, Lyndsay E. Reese, Ying Wang, Christine H. O'Connor, Annisa H. Rumahorbo, Kathryn L. Schwertfeger. Fibroblast growth factor receptor signaling modulates cholesterol storage in a SOAT1-dependent manner to promote mammary tumor cell invasion [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 6646.