TY - JOUR
T1 - Fibroblast growth factor receptor signaling modulates cholesterol storage in a SOAT1-dependent manner to promote mammary tumor cell invasion
AU - Tuokkola, Jennifer E.
AU - Reese, Lyndsay E.
AU - Wang, Ying
AU - O’Connor, Christine H.
AU - VanTreeck, Jillian G.
AU - Rumahorbo, Annisa H.
AU - Schwertfeger, Kathryn L.
N1 - Publisher Copyright:
© The Author(s) 2025.
PY - 2025/12
Y1 - 2025/12
N2 - 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, which correlates with reduced expression of matrix metalloproteinase expression. Furthermore, genetic knockdown of SOAT1 decreases mammary tumor growth in vivo. Taken together, these findings suggest a largely undiscovered metabolic role for FGFR signaling in regulating cholesterol metabolism in breast cancer and present a therapeutic vulnerability that could be targeted in FGFR-driven cancers.
AB - 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, which correlates with reduced expression of matrix metalloproteinase expression. Furthermore, genetic knockdown of SOAT1 decreases mammary tumor growth in vivo. Taken together, these findings suggest a largely undiscovered metabolic role for FGFR signaling in regulating cholesterol metabolism in breast cancer and present a therapeutic vulnerability that could be targeted in FGFR-driven cancers.
KW - Cholesterol metabolism
KW - Cholesterol storage
KW - Fibroblast growth factor
KW - Triple-negative breast cancer
UR - https://www.scopus.com/pages/publications/105010578287
UR - https://www.scopus.com/pages/publications/105010578287#tab=citedBy
U2 - 10.1186/s13058-025-02084-9
DO - 10.1186/s13058-025-02084-9
M3 - Article
C2 - 40665359
AN - SCOPUS:105010578287
SN - 1465-5411
VL - 27
JO - Breast Cancer Research
JF - Breast Cancer Research
IS - 1
M1 - 132
ER -
