ArticleOncotarget2016
PPARγ agonists promote differentiation of cancer stem cells by restraining YAP transcriptional activity.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 46 citations in OpenAlex.
- Different contributions of YAP1 and TAZ in the regulation of GIST tumorigenic properties.Cell communication and signaling : CCS · 2026Article
- Radiation-induced cellular plasticity primes glioblastoma for forskolin-mediated differentiation.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Targeting Lipid Metabolism in Cancer Stem Cells for Anticancer Treatment.International journal of molecular sciences · 2024Review
- Cancer stem cells: advances in knowledge and implications for cancer therapy.Signal transduction and targeted therapy · 2024Review
- Radiation-Induced Cellular Plasticity: A Strategy for Combatting Glioblastoma.bioRxiv : the preprint server for biology · 2024Article
- Review
- The role of peroxisome proliferator-activated receptors in the tumor microenvironment, tumor cell metabolism, and anticancer therapy.Frontiers in pharmacology · 2023Review
- Genetic Alterations and Deregulation of Hippo Pathway as a Pathogenetic Mechanism in Bone and Soft Tissue Sarcoma.Cancers · 2022Review
- Signaling pathways in the regulation of cancer stem cells and associated targeted therapy.MedComm · 2022Review
- Chemoresistance-Related Stem Cell Signaling in Osteosarcoma and Its Plausible Contribution to Poor Therapeutic Response: A Discussion That Still Matters.International journal of molecular sciences · 2022Review
- The Hippo pathway in cancer: YAP/TAZ and TEAD as therapeutic targets in cancer.Clinical science (London, England : 1979) · 2022Review
- CD44-positive cancer stem cells from oral squamous cell carcinoma exhibit reduced proliferation and stemness gene expression upon adipogenic induction.Medical oncology (Northwood, London, England) · 2022Article
- Article
- Review
- Article
- Direct conversion of osteosarcoma to adipocytes by targeting TNIK.JCI insight · 2021Article
- Pioglitazone modulates doxorubicin resistance in a in vivo model of drug resistant osteosarcoma xenograft.Naunyn-Schmiedeberg's archives of pharmacology · 2021Article
- PPARα-Selective Antagonist GW6471 Inhibits Cell Growth in Breast Cancer Stem Cells Inducing Energy Imbalance and Metabolic Stress.Biomedicines · 2021Article
- The regulatory networks of the Hippo signaling pathway in cancer development.Journal of Cancer · 2021Review
- Sarcoma treatment in the era of molecular medicine.EMBO molecular medicine · 2020Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors at 5 institutions in 1 country.
Funding
Abstract
Osteosarcoma (OS) is a highly aggressive pediatric bone cancer in which most tumor cells remain immature and fail to differentiate into bone-forming osteoblasts. However, OS cells readily respond to adipogenic stimuli suggesting they retain mesenchymal stem cell-like properties. Here we demonstrate that nuclear receptor PPARγ agonists such as the anti-diabetic, thiazolidinedione (TZD) drugs induce growth arrest and cause adipogenic differentiation in human, mouse and canine OS cells as well as in tumors in mice. Gene expression analysis reveals that TZDs induce lipid metabolism pathways while suppressing targets of the Hippo-YAP pathway, Wnt signaling and cancer-related proliferation pathways. Significantly, TZD action appears to be restricted to the high Sox2 expressing cancer stem cell population and is dependent on PPARγ expression. TZDs also affect growth and cell fate by causing the cytoplasmic sequestration of the transcription factors SOX2 and YAP that are required for tumorigenicity. Finally, we identify a TZD-regulated gene signature based on Wnt/Hippo target genes and PPARγ that predicts patient outcomes. Together, this work highlights a novel connection between PPARγ agonist in inducing adipogenesis and mimicking the tumor suppressive hippo pathway. It also illustrates the potential of drug repurposing for TZD-based differentiation therapy for osteosarcoma.
Indexed as
Identifiers
What OpenQuestion holds
Registered trials
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.