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

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 signaling 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 integrin expression and fibronectin binding 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 breast cancer. Mouse mammary epithelial cells (HC-11) expressing a chemically inducible FGFR1 were treated with B/B homodimerizer for 2 hours prior to RNA extraction. Control samples were treated with a solvent control for the same amount of time.