ArticleCancer letters2015
Inhibition of angiogenesis by selective estrogen receptor modulators through blockade of cholesterol trafficking rather than estrogen receptor antagonism.
Article in Cancer letters, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 26 citations in OpenAlex.
- Ternary Complex Components Responsible for Rapid LDL Internalization as Biomarkers for Breast Cancer Associated with Proliferation and Early Recurrence.Cancer research communications · 2025Article
- Exogenous estrogen partially rescues progesterone deficiency and autophagosome enlargement inReproductive and developmental medicine · 2024Article
- Tubeimosides are pan-coronavirus and filovirus inhibitors that can block their fusion protein binding to Niemann-Pick C1.Nature communications · 2024Article
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Inhibition of squalene epoxidase linking with PI3K/AKT signaling pathway suppresses endometrial cancer.Cancer science · 2023Article
- TFEB controls integrin-mediated endothelial cell adhesion by the regulation of cholesterol metabolism.Angiogenesis · 2022Article
- Developmental malformations resulting from high-dose maternal tamoxifen exposure in the mouse.PloS one · 2021Article
- Review
- Angiogenesis Changes in Ovariectomized Rats with Osteoporosis Treated with Estrogen Replacement Therapy.BioMed research international · 2019Article
- Astemizole Inhibits mTOR Signaling and Angiogenesis by Blocking Cholesterol Trafficking.International journal of biological sciences · 2018Article
- Pharmacological blockade of cholesterol trafficking by cepharanthine in endothelial cells suppresses angiogenesis and tumor growth.Cancer letters · 2017Article
- Selective inhibition of Ebola entry with selective estrogen receptor modulators by disrupting the endolysosomal calcium.Scientific reports · 2017Article
- Identification ofGenes & cancer · 2016Article
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Selective estrogen receptor modulators (SERM) including tamoxifen are known to inhibit angiogenesis. However, the underlying mechanism, which is independent of their action on the estrogen receptor (ER), has remained largely unknown. In the present study, we found that tamoxifen and other SERM inhibited cholesterol trafficking in endothelial cells, causing a hyper-accumulation of cholesterol in late endosomes/lysosomes. Inhibition of cholesterol trafficking by tamoxifen was accompanied by abnormal subcellular distribution of vascular endothelial growth factor receptor-2 (VEGFR2) and inhibition of the terminal glycosylation of the receptor. Tamoxifen also caused perinuclear positioning of lysosomes, which in turn trapped the mammalian target of rapamycin (mTOR) in the perinuclear region of endothelial cells. Abnormal distribution of VEGFR2 and mTOR and inhibition of VEGFR2 and mTOR activities by tamoxifen were significantly reversed by addition of cholesterol-cyclodextrin complex to the culture media of endothelial cells. Moreover, high concentrations of tamoxifen inhibited endothelial and breast cancer cell proliferation in a cholesterol-dependent, but ER-independent, manner. Together, these results unraveled a previously unrecognized mechanism of angiogenesis inhibition by tamoxifen and other SERM, implicating cholesterol trafficking as an attractive therapeutic target for cancer treatment.
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