ArticleOncogene2013
Inverse PPARβ/δ agonists suppress oncogenic signaling to the ANGPTL4 gene and inhibit cancer cell invasion.
Article in Oncogene, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 87 citations in OpenAlex.
- Inhibitory role of angiopoietin‑like 4 for cancer progression in oropharyngeal squamous cell carcinoma.Oncology reports · 2026Article
- PPARδ: An underappreciated tumor accelerator in pancreatic ductal adenocarcinoma.Cancer letters · 2026Review
- Erucic Acid, Derived by Lactobacillus Crispatus, Induces Ferroptosis in Cervical Cancer Organoids Through the PPAR-δ Signaling Pathway.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Adipocytes-induced ANGPTL4/KLF4 axis drives glycolysis and metastasis in triple-negative breast cancer.Journal of experimental & clinical cancer research : CR · 2025Article
- Carboxylesterase 1 regulates peroxisome proliferator-activated receptor gamma to inhibit the growth and metastasis of breast cancer cells.Journal of molecular histology · 2025Article
- Emerging roles of angiopoietin‑like 4 in human tumors (Review).International journal of oncology · 2025Review
- Adipose Factor ANGPTL4: Its Role in Aging Mechanisms and Associated Diseases.Clinical interventions in aging · 2025Review
- Article
- ANGPTL4 Suppresses Clear Cell Renal Cell Carcinoma via Inhibition of Lysosomal Acid Lipase.Cancer research communications · 2024Article
- Nervonic Acid Inhibits Replicative Senescence of Human Wharton's Jelly-Derived Mesenchymal Stem Cells.International journal of stem cells · 2024Article
- Article
- Article
- The Role of PPARs in Breast Cancer.Cells · 2022Review
- Angiopoietin-Like Protein 4 Is Involved in Manganese Superoxide Dismutase-Mediated Suppression of Breast Cancer Cell Growth.Bulletin of experimental biology and medicine · 2022Article
- Rapid acceleration of KRAS-mutant pancreatic carcinogenesis via remodeling of tumor immune microenvironment by PPARδ.Nature communications · 2022Article
- Angiopoietin-Like Protein 4 and Insulin-Like Growth Factor-1 Expression in Invasive Breast Carcinoma in Young Women.Pathophysiology : the official journal of the International Society for Pathophysiology · 2022Article
- Genomic Insights into Non-steroidal Nuclear Receptors in Prostate and Breast Cancer.Advances in experimental medicine and biology · 2022Article
- In Silico Identification of Novel Interactions for FABP5 (Fatty Acid-Binding Protein 5) with Nutraceuticals: Possible Repurposing Approach.Advances in experimental medicine and biology · 2021Article
- Mining the role of angiopoietin-like protein family in gastric cancer and seeking potential therapeutic targets by integrative bioinformatics analysis.Cancer medicine · 2020Article
- Targeting TRAF3IP2, Compared to Rab27, is More Effective in Suppressing the Development and Metastasis of Breast Cancer.Scientific reports · 2020Article
Corrections and comments
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Authors and funding
18 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Besides its established functions in intermediary metabolism and developmental processes, the nuclear receptor peroxisome proliferator-activated receptor β/δ (PPARβ/δ) has a less defined role in tumorigenesis. In the present study, we have identified a function for PPARβ/δ in cancer cell invasion. We show that two structurally divergent inhibitory ligands for PPARβ/δ, the inverse agonists ST247 and DG172, strongly inhibit the serum- and transforming growth factor β (TGFβ)-induced invasion of MDA-MB-231 human breast cancer cells into a three-dimensional matrigel matrix. To elucidate the molecular basis of this finding, we performed chromatin immunoprecipitation sequencing (ChIP-Seq) and microarray analyses, which identified the gene encoding angiopoietin-like 4 (ANGPTL4) as the major transcriptional PPARβ/δ target in MDA-MB-231 cells, previously implicated in TGFβ-mediated tumor progression and metastatic dissemination. We show that the induction of ANGPTL4 by TGFβ and other oncogenic signals is strongly repressed by ST247 and DG172 in a PPARβ/δ-dependent fashion, resulting in the inhibition of ANGPTL4 secretion. This effect is attributable to these ligands' ability to induce a dominant transcriptional repressor complex at the site of transcription initiation that blocks preinitiation complex formation through an histone deacetylase-independent, non-canonical mechanism. Repression of ANGPTL4 transcription by inverse PPARβ/δ agonists is functionally linked to the inhibition of cancer cell invasion into a three-dimensional matrix, as (i) invasion of MDA-MB-231 cells is critically dependent on ANGPTL4 expression, (ii) recombinant ANGPTL4 stimulates invasion, and (iii) reverses the inhibitory effect of ST247 and DG172. These findings indicate that a PPARβ/δ-ANGPTL4 pathway is involved in the regulation of tumor cell invasion and that its pharmacological manipulation by inverse PPARβ/δ agonists is feasible.
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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 OpenQuestion graph.