ArticleCell death and differentiation2020
The lipogenic LXR-SREBF1 signaling pathway controls cancer cell DNA repair and apoptosis and is a vulnerable point of malignant tumors for cancer therapy.
Article in Cell death and differentiation, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 22 papers, 1 of them a synthesis that pooled it.
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Who cites it
22 citing papers in PubMed, 1 synthesis or guideline pooled it, 38 citations in OpenAlex.
- Mechanisms of obesity- and diabetes mellitus-related pancreatic carcinogenesis: a comprehensive and systematic review.Signal transduction and targeted therapy · 2023Pooled it
- Triptonide enhances DNA damage by inhibiting TRIP13‑mediated DNA repair and synergizes with bortezomib to suppress multiple myeloma.International journal of oncology · 2026Article
- Epigenetic modifications in cancer drug resistance: molecular mechanisms and therapeutic interventions.Molecular biomedicine · 2026Review
- Chicoric acid enhanced brain cholesterol efflux and reduced Aβ pathology via LXR-ABCA1 signaling in Alzheimer's models.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2026Article
- Variations in DNA Repair Genes and Intratumoral Genetic Heterogeneity in Temozolomide-Resistant Glioblastoma.Human mutation · 2026Article
- Unlocking the lipid code: SREBPs as key drivers in gastrointestinal tumour metabolism.Lipids in health and disease · 2025Review
- Liver X receptor agonist T0901317 alleviates sepsis-induced acute lung injury by enhancing macrophage autophagy.Frontiers in pharmacology · 2025Article
- Enhanced cancer cell proliferation and aggressive phenotype counterbalance in breast cancer with high BRCA1 gene expression.Breast cancer research and treatment · 2024Article
- Autocorrelation analysis of a phenotypic screen reveals hidden drug activity.Scientific reports · 2024Article
- Cancer/testis-45A1 promotes cervical cancer cell tumorigenesis and drug resistance by activating oncogenic SRC and downstream signaling pathways.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Lipid Metabolism as a Potential Target of Liver Cancer.Journal of hepatocellular carcinoma · 2024Review
- Liver X Receptors (LXRs) in cancer-an Eagle's view on molecular insights and therapeutic opportunities.Frontiers in cell and developmental biology · 2024Review
- Article
- Liver X receptors induce antiproliferative effects in basal-like breast cancer.Molecular oncology · 2023Article
- Emerging Insights into Liver X Receptor α in the Tumorigenesis and Therapeutics of Human Cancers.Biomolecules · 2023Review
- The long non-coding RNA keratin-7 antisense acts as a new tumor suppressor to inhibit tumorigenesis and enhance apoptosis in lung and breast cancers.Cell death & disease · 2023Article
- The Cancer/Testis Antigen CT45A1 Promotes Transcription of OncogenicJournal of breast cancer · 2023Article
- Lipid metabolism in pancreatic cancer: emerging roles and potential targets.Cancer communications (London, England) · 2022Review
- The Impact of Oxidative Stress and AKT Pathway on Cancer Cell Functions and Its Application to Natural Products.Antioxidants (Basel, Switzerland) · 2022Review
- Targeting SREBP-1-Mediated Lipogenesis as Potential Strategies for Cancer.Frontiers in oncology · 2022Review
Corrections and comments
- Erratum issued
Authors and funding
15 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer cells are defective in DNA repair, so they experience increased DNA strand breaks, genome instability, gene mutagenesis, and tumorigenicity; however, multiple classic DNA repair genes and pathways are strongly activated in malignant tumor cells to compensate for the DNA repair deficiency and gain an apoptosis resistance. The mechanisms underlying this phenomenon in cancer are unclear. We speculate that a key DNA repair gene or signaling pathway in cancer has not yet been recognized. Here, we show that the lipogenic liver X receptor (LXR)-sterol response element binding factor-1 (SREBF1) axis controls the transcription of a key DNA repair gene polynucleotide kinase/phosphatase (PNKP), thereby governing cancer cell DNA repair and apoptosis. Notably, the PNKP levels were significantly reduced in 95% of human pancreatic cancer (PC) patients, particularly deep reduction for sixfold in all of the advanced-stage PC cases. PNKP is also deficient in three other types of cancer that we examined. In addition, the expression of LXRs and SREBF1 was significantly reduced in the tumor tissues from human PC patients compared with the adjacent normal tissues. The newly identified LXR-SREBF1-PNKP signaling pathway is deficient in PC, and the defect in the pathway contributes to the DNA repair deficiency in the cancer. Strikingly, further diminution of the vulnerable LXR-SREBF1-PNKP signaling pathway using a small molecule triptonide, a new LXR antagonist identified in this investigation, at a concentration of 8 nM robustly activated tumor-suppressor p53 and readily elevated cancer cell DNA strand breaks over an apoptotic threshold, and selectively induced PC cell apoptosis, resulting in almost complete elimination of tumors in xenograft mice without obvious complications. Our findings provide new insight into DNA repair and apoptosis in cancer, and offer a new platform for developing novel anticancer therapeutics.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.