ArticleOncogene2018
Activation of PPARα by clofibrate sensitizes pancreatic cancer cells to radiation through the Wnt/β-catenin pathway.
Article in Oncogene, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 40 papers, 1 of them a synthesis that pooled it.
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Who cites it
40 citing papers in PubMed, 1 synthesis or guideline pooled it, 56 citations in OpenAlex.
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- CYP4X1/sEH-Dependent Endocannabinoid Metabolism Drives Fibroblast-Mediated Immunosuppression to Limit Immunotherapy in Colon Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Targeting PPARα activation sensitizes glioblastoma cells to temozolomide and reverses acquired resistance by inhibiting H3K18 lactylation.Acta pharmacologica Sinica · 2025Article
- Pharmacological inhibition of Peroxisome Proliferation-Activated Receptor Delta (PPARδ) imparts selective leukemia cell death.Cancer & metabolism · 2025Article
- Nuclear receptors as novel regulators that modulate cancer radiosensitivity and normal tissue radiotoxicity.Molecular cancer · 2025Review
- Mechanisms of GPM6A in Malignant Tumors.Cancer reports (Hoboken, N.J.) · 2025Review
- The Role of PLIN3 in Prognosis and Tumor-Associated Macrophage Infiltration: A Pan-Cancer Analysis.Journal of inflammation research · 2025Article
- Genome wide-scale CRISPR-Cas9 knockout screens identify a fitness score for optimized risk stratification in colorectal cancer.Journal of translational medicine · 2024Article
- Integration of machine learning and experimental validation to identify the prognostic signature related to diverse programmed cell deaths in breast cancer.Frontiers in oncology · 2024Article
- Single-cell RNA-Seq analysis of molecular changes during radiation-induced skin injury: the involvement of Nur77.Theranostics · 2024Article
- Protein Tyrosine Phosphatase Receptor Zeta 1 as a Potential Target in Cancer Therapy and Diagnosis.International journal of molecular sciences · 2023Review
- The Roles of Secreted Wnt Ligands in Cancer.International journal of molecular sciences · 2023Review
- Epigenetic drugs in somatostatin type 2 receptor radionuclide theranostics and radiation transcriptomics in mouse pheochromocytoma models.Theranostics · 2023Article
- The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy.Frontiers in pharmacology · 2023Review
- Review
- HNRNPC regulates RhoA to induce DNA damage repair and cancer-associated fibroblast activation causing radiation resistance in pancreatic cancer.Journal of cellular and molecular medicine · 2022Article
- SIRT3 and Metabolic Reprogramming Mediate the Antiproliferative Effects of Whey in Human Colon Cancer Cells.Cancers · 2021Article
- LINC00261 elevation inhibits angiogenesis and cell cycle progression of pancreatic cancer cells by upregulating SCP2 via targeting FOXP3.Journal of cellular and molecular medicine · 2021Article
- lncRNA Ttc3-209 Promotes the Apoptosis of Retinal Ganglion Cells in Retinal Ischemia Reperfusion Injury by Targeting the miR-484/Wnt8a Axis.Investigative ophthalmology & visual science · 2021Article
Corrections and comments
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Authors and funding
12 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Radiotherapy is emerging as an important modality for the local control of pancreatic cancer, but pancreatic cancer cell radioresistance remains a serious concern. Peroxisome proliferator-activated receptor α (PPARα) is a member of the PPAR nuclear hormone receptor superfamily, which can be activated by fibrate ligands. The clinical relevance of PPARα and its biological function in pancreatic cancer radiosensitivity have not been previously described. In this study, we examined PPARα expression in tissue samples of pancreatic cancer patients. We found significantly higher expression of PPARα in pancreatic cancer tissues than in tumor-adjacent tissues and that the PPARα expression level is inversely associated with higher overall patient survival rate. We further observed that PPARα activation by its agonist clofibrate sensitizes pancreatic cancer cells to radiation by modulating cell cycle progression and apoptosis in several pancreatic cancer cell lines. Small interfering RNA-mediated PPARα silencing and PPARα blockade by the antagonist GW6471 abolish the effect of clofibrate on radiosensitization. An in vivo study showed that PANC1 xenografts treated with clofibrate are more sensitive to radiation than untreated xenografts. mRNA profiling by microarray analysis revealed that the expression of PTPRZ1 and Wnt8a, two core components of the β-catenin pathway, is downregulated by clofibrate. Chromatin immunoprecipitation analysis confirmed that clofibrate abrogates the binding of nuclear factor-κB to the PTPRZ1 and Wnt8a promoters, ultimately decreasing Wnt/β-catenin signaling activity, which is associated with radiosensitivity. Overall, we demonstrate that PPARα is overexpressed in pancreatic cancer tissues and clofibrate-mediated PPARα activation sensitizes pancreatic cancer cells to radiation through the Wnt/β-catenin pathway.
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