ArticleMolecular cancer therapeutics2014
Activation of liver X receptors inhibits hedgehog signaling, clonogenic growth, and self-renewal in multiple myeloma.
Article in Molecular cancer therapeutics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- The long non-coding RNA CRNDE stabilises SIRT1 protein and influences Hedgehog signalling in multiple myeloma.Leukemia · 2025Article
- Nestin in multiple myeloma: emerging insights into a potential therapeutic target.Frontiers in oncology · 2025Review
- Identification of a cholesterol metabolism-related prognostic signature for multiple myeloma.Scientific reports · 2023Article
- Lipid metabolic vulnerabilities of multiple myeloma.Clinical and experimental medicine · 2023Review
- LXR inhibitor SR9243-loaded immunoliposomes modulate lipid metabolism and stemness in colorectal cancer cells.Medical oncology (Northwood, London, England) · 2023Article
- Hedgehog Signaling in Myeloid Malignancies.Cancers · 2021Review
- Patched regulates lipid homeostasis by controlling cellular cholesterol levels.Nature communications · 2021Article
- Modulation of LXR signaling altered the dynamic activity of human colon adenocarcinoma cancer stem cells in vitro.Cancer cell international · 2021Article
- Cholesterol Metabolic Reprogramming in Cancer and Its Pharmacological Modulation as Therapeutic Strategy.Frontiers in oncology · 2021Review
- Activation of liver X receptor delayed the retinal degeneration of rd1 mice through modulation of the immunological function of glia.Oncotarget · 2017Article
- Article
- Small hepatocyte-like progenitor cells may be a Hedgehog signaling pathway-controlled subgroup of liver stem cells.Experimental and therapeutic medicine · 2016Article
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- Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice.Scientific reports · 2016Article
- Targeting liver X receptors in cancer therapeutics.Nature reviews. Cancer · 2015Review
- Drug metabolism and clearance system in tumor cells of patients with multiple myeloma.Oncotarget · 2015Article
- Article
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
The Hedgehog (Hh) signaling pathway is aberrantly activated in a wide variety of human cancers, and recent clinical studies have demonstrated that pathway inhibitors are effective in advanced basal cell carcinoma (BCC). The majority of these agents have been designed to target SMOOTHENED (SMO), a transmembrane regulator of Hh signaling, but subsequent mutations in SMO have been found to generate drug resistance. In other cancers, oncogenic events that bypass SMO may activate canonical Hh signaling, and SMO antagonists have not demonstrated significant activity in several diseases. Therefore, alternative strategies targeting the Hh pathway downstream of SMO may have clinical utility. Liver X receptors (LXR) regulate cholesterol and fatty acid homeostasis, and LXR activation can inhibit the Hh pathway in normal mouse embryonic fibroblasts. We examined the effects of LXR activation on Hh signaling in human multiple myeloma cells and found that LXR agonists inhibited Hh pathway activity and clonogenic tumor growth in vitro. LXR activation also inhibited putative multiple myeloma cancer stem cells in vivo leading to the loss of tumor initiating and self-renewal potential. Finally, Hh signaling was inhibited downstream of SMO, suggesting that LXR agonists may represent a novel strategy to target pathogenic Hh signaling as well as treat multiple myeloma.
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