ArticleThe Journal of experimental medicine2016
Notch activation drives adipocyte dedifferentiation and tumorigenic transformation in mice.
Article in The Journal of experimental medicine, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
What it found
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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.
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Who cites it
64 citing papers in PubMed, 101 citations in OpenAlex.
- Tumorigenesis of well-differentiated and dedifferentiated liposarcoma: 12q amplicon architecture, oncogenic cargo, and evolutionary progression.Cancer metastasis reviews · 2026Review
- Notch signaling regulates the secretion of pro-metastatic factors in extracellular vesicles in liposarcoma.Cancer letters · 2026Article
- Molecular mechanisms underlying liposarcoma subtype transition and proteasome-associated targeted interventions.Journal of translational medicine · 2026Review
- Dedifferentiation of Mature Adipocytes and Their Future Potential for Regenerative Medicine Applications.Biomedicines · 2026Review
- NOTCH Signaling Networks in Perivascular Adipose Tissue.Arteriosclerosis, thrombosis, and vascular biology · 2025Review
- Characterization of subcutaneous and visceral de-differentiated fat cells.Molecular metabolism · 2025Article
- Three-dimensional models: from cell culture to Patient-Derived Organoid and its application to future liposarcoma research.Oncology research · 2025Review
- Bone marrow adipocytes: key players in vascular niches, aging, and disease.Frontiers in cell and developmental biology · 2025Review
- Integrated lipidomics and RNA-seq reveal prognostic biomarkers in well-differentiated and dedifferentiated retroperitoneal liposarcoma.Cancer cell international · 2024Article
- Adipose Tissue Plasticity: A Comprehensive Definition and Multidimensional Insight.Biomolecules · 2024Review
- Review
- PAQR4 regulates adipocyte function and systemic metabolic health by mediating ceramide levels.Nature metabolism · 2024Article
- The Notch-PDGFRβ axis suppresses brown adipocyte progenitor differentiation in early post-natal mice.Developmental cell · 2024Article
- A Notch toward Progenitor D(G)FRentiation: Defining a NOTCH-PDGFR axis in brown adipogenesis.Developmental cell · 2024Article
- Dysfunctional adipocytes promote tumor progression through YAP/TAZ-dependent cancer-associated adipocyte transformation.Nature communications · 2024Article
- Sex-dependent Prognosis of Patients with Advanced Soft Tissue Sarcoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Article
- Next-Cell Hypothesis: Mechanism of Obesity-Associated Carcinogenesis.Advances in experimental medicine and biology · 2024Review
- Article
- Unraveling the intricate relationship between lipid metabolism and oncogenic signaling pathways.Frontiers in cell and developmental biology · 2024Review
- Article
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 1 institution in 1 country.
Funding
Abstract
Liposarcomas (LPSs) are the most common soft-tissue cancer. Because of the lack of animal models, the cellular origin and molecular regulation of LPS remain unclear. Here, we report that mice with adipocyte-specific activation of Notch signaling (Ad/N1ICD) develop LPS with complete penetrance. Lineage tracing confirms the adipocyte origin of Ad/N1ICD LPS. The Ad/N1ICD LPS resembles human dedifferentiated LPS in histological appearance, anatomical localization, and gene expression signature. Before transformation, Ad/N1ICD adipocytes undergo dedifferentiation that leads to lipodystrophy and metabolic dysfunction. Although concomitant Pten deletion normalizes the glucose metabolism of Ad/N1ICD mice, it dramatically accelerates the LPS prognosis and malignancy. Transcriptomes and lipidomics analyses indicate that Notch activation suppresses lipid metabolism pathways that supply ligands to Pparγ, the master regulator of adipocyte homeostasis. Accordingly, synthetic Pparγ ligand supplementation induces redifferentiation of Ad/N1ICD adipocytes and tumor cells, and prevents LPS development in Ad/N1ICD mice. Importantly, the Notch target HES1 is abundantly expressed in human LPS, and Notch inhibition suppresses the growth of human dedifferentiated LPS xenografts. Collectively, ectopic Notch activation is sufficient to induce dedifferentiation and tumorigenic transformation of mature adipocytes in mouse.
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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.