ArticleCell death & disease2019
Targeting the transcription factor receptor LXR to treat clear cell renal cell carcinoma: agonist or inverse agonist?
Article in Cell death & disease, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers, 1 of them a synthesis that pooled it.
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Who cites it
54 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Cholesterol homeostasis and cancer: a new perspective on the low-density lipoprotein receptor.Cellular oncology (Dordrecht, Netherlands) · 2022Pooled it
- Targeting USP8 with odoroside A regulates LXRβ-mediated fatty acid metabolic reprogramming against colorectal cancer.Acta pharmacologica Sinica · 2026Article
- Integrated multi-omics analysis of neutrophil extracellular trap-related genes in renal cell carcinoma using bioinformatics and machine learning.Discover oncology · 2026Article
- Sino-C, a novel sinomenine derivative, induces cell death by disrupting cholesterol homeostasis in colorectal cancer cells.Acta pharmacologica Sinica · 2026Article
- Comprehensive analysis of key palmitoylation-modifying enzymes in clear cell renal cell carcinoma: implications for prognosis and therapy.Cancer cell international · 2026Article
- Lipid reprogramming and ferroptosis crosstalk in clear cell renal cell carcinoma: metabolic vulnerabilities and therapeutic targeting.Molecular cancer · 2025Review
- Targeting cholesterol metabolism: a promising therapy strategy for cancer.Acta pharmacologica Sinica · 2025Review
- IGFBP1 orchestrates metabolic reprogramming to drive clear cell renal cell carcinoma progression through NR1H4-mediated lipid homeostasis disruption.Cancer cell international · 2025Article
- Unveiling the crossroads of STING signaling pathway and metabolic reprogramming: the multifaceted role of the STING in the TME and new prospects in cancer therapies.Cell communication and signaling : CCS · 2025Review
- Discovery of paradoxical genes: reevaluating the prognostic impact of overexpressed genes in cancer.Frontiers in cell and developmental biology · 2025Review
- Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024Review
- Cholesterol Metabolism and Urinary System Tumors.Biomedicines · 2024Review
- Bile Acid Metabolism Mediates Cholesterol Homeostasis and Promotes Tumorigenesis in Clear Cell Renal Cell Carcinoma.Cancer research · 2024Article
- Cholesterol homeostasis confers glioma malignancy triggered by hnRNPA2B1-dependent regulation of SREBP2 and LDLR.Neuro-oncology · 2024Article
- Review
- Plasma proteome fingerprint in kidney diseases.Frontiers in molecular biosciences · 2024Article
- Cholesterol metabolism in tumor microenvironment: cancer hallmarks and therapeutic opportunities.International journal of biological sciences · 2024Review
- Review
- Functional significance of cholesterol metabolism in cancer: from threat to treatment.Experimental & molecular medicine · 2023Review
- The mechanism of liver X receptor regulates the balance of glycoFAsynthesis and cholesterol synthesis in clear cell renal cell carcinoma.Clinical and translational medicine · 2023Article
Corrections and comments
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Authors and funding
7 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Growing evidence indicates that clear cell renal cell carcinoma (ccRCC) is a metabolism-related disease. Changes in fatty acid (FA) and cholesterol metabolism play important roles in ccRCC development. As a nuclear transcription factor receptor, Liver X receptor (LXR) regulates a variety of key molecules associated with FA synthesis and cholesterol transport. Therefore, targeting LXR may provide new therapeutic targets for ccRCC. However, the potential regulatory effect and molecular mechanisms of LXR in ccRCC remain unknown. In the present study, we found that both an LXR agonist and an XLR inverse agonist could inhibit proliferation and colony formation and induce apoptosis in ccRCC cells. We observed that the LXR agonist LXR623 downregulated the expression of the low-density lipoprotein receptor (LDLR) and upregulated the expression of ABCA1, which resulted in reduced intracellular cholesterol and apoptosis. The LXR inverse agonist SR9243 downregulated the FA synthesis proteins sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FASN) and stearoyl-coA desaturase 1 (SCD1), causing a decrease in intracellular FA content and inducing apoptosis in ccRCC cells. SR9243 and LXR623 induced apoptosis in ccRCC cells but had no killing effect on normal renal tubular epithelial HK2 cells. We also found that SRB1-mediated high-density lipoprotein (HDL) in cholesterol influx is the cause of high cholesterol in ccRCC cells. In conclusion, our data suggest that an LXR inverse agonist and LXR agonist decrease the intracellular FA and cholesterol contents in ccRCC to inhibit tumour cells but do not have cytotoxic effects on non-malignant cells. Thus, LXR may be a safe therapeutic target for treating ccRCC patients.
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