ArticleScientific reports2016
Activated FXR Inhibits Leptin Signaling and Counteracts Tumor-promoting Activities of Cancer-Associated Fibroblasts in Breast Malignancy.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 2 of them syntheses that pooled it.
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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
43 citing papers in PubMed, 2 syntheses or guidelines pooled it, 60 citations in OpenAlex.
- Pooled it
- Leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Pooled it
- Adipocyte-derived estrogen signaling influences TROP2 expression in ERα-positive breast cancer.Frontiers in endocrinology · 2026Article
- SOCS3: An Immunological Biomarker Offering Potential Therapeutic Targets for Malignant Tumors.Biological procedures online · 2025Review
- Farnesoid X receptor‑driven metabolic plasticity: Bridging physiological adaptation and malignant transformation in lipid handling (Review).International journal of molecular medicine · 2025Review
- Adipocyte/Tumor cell crosstalk via IGF-1/TXNIP axis promotes malignancy and endocrine resistance in breast cancer.Cell communication and signaling : CCS · 2025Article
- Hepatic Nuclear Receptors in Cholestasis-to-Cholangiocarcinoma Pathology.The American journal of pathology · 2025Review
- FXR Agonism with Bile Acid Mimetic Reduces Pre-Clinical Triple-Negative Breast Cancer Burden.Cancers · 2024Article
- Targeting Farnesoid X Receptor in Tumor and the Tumor Microenvironment: Implication for Therapy.International journal of molecular sciences · 2023Review
- Role of Leptin and Adiponectin in Carcinogenesis.Cancers · 2023Review
- Solid Lipid Nanoparticles Hydroquinone-Based for the Treatment of Melanoma: Efficacy and Safety Studies.Pharmaceutics · 2023Article
- Repurposing FDA-approved drugs as FXR agonists: a structure based in silico pharmacological study.Bioscience reports · 2023Article
- Fibroblasts as Turned Agents in Cancer Progression.Cancers · 2023Review
- Antioxidant and Anti-Inflammatory Effects of Extracts from Pulsed Electric Field-Treated Artichoke By-Products in Lipopolysaccharide-Stimulated Human THP-1 Macrophages.Foods (Basel, Switzerland) · 2022Article
- Nuclear Receptors and Lipid Sensing.Advances in experimental medicine and biology · 2022Article
- Design, synthesis and cytotoxic evaluation of novel betulonic acid-diazine derivatives as potential antitumor agents.Frontiers in chemistry · 2022Article
- Review
- Novel Insights into the Antagonistic Effects of Losartan against Angiotensin II/AGTR1 Signaling in Glioblastoma Cells.Cancers · 2021Article
- Targeting Farnesoid X receptor (FXR) for developing novel therapeutics against cancer.Molecular biomedicine · 2021Review
- Hampering Stromal Cells in the Tumor Microenvironment as a Therapeutic Strategy to Destem Cancer Stem Cells.Cancers · 2021Review
Corrections and comments
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs), the principal components of the tumor stroma, play a central role in cancer development and progression. As an important regulator of the crosstalk between breast cancer cells and CAFs, the cytokine leptin has been associated to breast carcinogenesis. The nuclear Farnesoid X Receptor-(FXR) seems to exert an oncosuppressive role in different tumors, including breast cancer. Herein, we demonstrated, for the first time, that the synthetic FXR agonist GW4064, inhibiting leptin signaling, affects the tumor-promoting activities of CAFs in breast malignancy. GW4064 inhibited growth, motility and invasiveness induced by leptin as well as by CAF-conditioned media in different breast cancer cell lines. These effects rely on the ability of activated FXR to increase the expression of the suppressor of the cytokine signaling 3 (SOCS3) leading to inhibition of leptin-activated signaling and downregulation of leptin-target genes. In vivo xenograft studies, using MCF-7 cells alone or co-injected with CAFs, showed that GW4064 administration markedly reduced tumor growth. Interestingly, GW4064-treated tumors exhibited decreased levels of leptin-regulated proteins along with a strong staining intensity for SOCS3. Thus, FXR ligands might represent an emerging potential anti-cancer therapy able to block the tumor supportive role of activated fibroblasts within the breast microenvironment.
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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.