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

IF 5.6 1区 医学 Q1 Medicine
Jennifer E Tuokkola, Lyndsay E Reese, Ying Wang, Christine H O'Connor, Jillian G VanTreeck, Annisa H Rumahorbo, Kathryn L Schwertfeger
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引用次数: 0

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, 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.

成纤维细胞生长因子受体信号以soat1依赖的方式调节胆固醇储存,促进乳腺肿瘤细胞侵袭。
由成纤维细胞生长因子受体(FGFRs)发出的信号在高达85%的乳腺癌中活跃,并导致肿瘤细胞的增殖、迁移和侵袭增强。在这里,我们表明FGFR信号调节乳腺癌中的胆固醇代谢。具体来说,我们证明了FGFR激活通过上调甾醇o -酰基转移酶1 (SOAT1)的表达来促进细胞胆固醇储存。此外,我们证明SOAT1的抑制减弱了fgfr驱动的肿瘤细胞中的集落形成和侵袭,这与基质金属蛋白酶表达的降低有关。此外,SOAT1基因敲低可抑制体内乳腺肿瘤的生长。综上所述,这些发现表明FGFR信号在调节乳腺癌中胆固醇代谢中的代谢作用在很大程度上未被发现,并且在FGFR驱动的癌症中存在治疗脆弱性。
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来源期刊
CiteScore
12.00
自引率
0.00%
发文量
76
审稿时长
12 weeks
期刊介绍: Breast Cancer Research, an international, peer-reviewed online journal, publishes original research, reviews, editorials, and reports. It features open-access research articles of exceptional interest across all areas of biology and medicine relevant to breast cancer. This includes normal mammary gland biology, with a special emphasis on the genetic, biochemical, and cellular basis of breast cancer. In addition to basic research, the journal covers preclinical, translational, and clinical studies with a biological basis, including Phase I and Phase II trials.
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