ArticleCancer & metabolism2020
Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells.
Article in Cancer & metabolism, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 19 citations in OpenAlex.
- Mitochondrial uncoupling, energy substrate utilization, and brown adipose tissue as therapeutic targets in cancer.npj metabolic health and disease · 2025Review
- Downregulation of uncoupling protein 1 by hypermethylation in gastric cancer activatesWorld journal of gastrointestinal oncology · 2025Article
- Defining hypoxia in cancer: A landmark evaluation of hypoxia gene expression signatures.Cell genomics · 2025Article
- Tunable Self-Referenced Molecular Thermometers via Manipulation of Dual Emission in Platinum(II) Pyridinedipyrrolide Complexes.ACS applied materials & interfaces · 2024Article
- Probing organoid metabolism using fluorescence lifetime imaging microscopy (FLIM): The next frontier of drug discovery and disease understanding.Advanced drug delivery reviews · 2023Review
- FABP7: a glial integrator of sleep, circadian rhythms, plasticity, and metabolic function.Frontiers in systems neuroscience · 2023Article
- Mitochondrial Protein UCP1 Inhibits the Malignant Behaviors of Triple-negative Breast Cancer through Activation of Mitophagy and Pyroptosis.International journal of biological sciences · 2022Article
- Identification of UCP1 and UCP2 as Potential Prognostic Markers in Breast Cancer: A Study Based on Immunohistochemical Analysis and Bioinformatics.Frontiers in cell and developmental biology · 2022Article
- The subtype-specific molecular function of SPDEF in breast cancer and insights into prognostic significance.Journal of cellular and molecular medicine · 2021Article
- Luminescence lifetime imaging of three-dimensional biological objects.Journal of cell science · 2021Article
- Increased demand for NADMolecular cell · 2021Article
- Cancer Stem Cell-Associated Pathways in the Metabolic Reprogramming of Breast Cancer.International journal of molecular sciences · 2020Review
- Correction to: Disruption of hypoxia-inducible fatty acid binding protein 7 induces beige fat-like differentiation and thermogenesis in breast cancer cells.Cancer & metabolism · 2020Article
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
Abstract
backgroundHumans produce heat through non-shivering thermogenesis, a metabolic process that occurs in inducible beige adipocytes expressing uncoupling protein 1 (UCP1). UCP1 dissipates the proton gradient of the mitochondrial inner membrane and converts that energy into heat. It is unclear whether cancer cells can exhibit autonomous thermogenesis. Previously, we found that the knockdown of hypoxia-inducible fatty acid binding protein 7 (FABP7) increased reactive oxygen species (ROS) in breast cancer cells. ROS are known to induce beige adipocyte differentiation.
methodsWe investigated the association of tumor hypoxia, FABP7, and UCP1 across breast cancer patients using METABRIC and TCGA data sets. Furthermore, using a breast cancer cell line, HCC1806, we tested the effect of FABP7 knockdown on cellular physiology including thermogenesis.
resultsWe found a strong mutual exclusivity of FABP7 and UCP1 expression both in METABRIC and in TCGA, indicating major metabolic phenotypic differences. FABP7 was preferentially distributed in poorly differentiated-, estrogen receptor (ER) negative tumors. In contrast, UCP1 was highly expressed in normal ducts and well-differentiated-, ER positive-, less hypoxic tumors. In the cell line-based experiments, UCP1 and its transcriptional regulators were upregulated upon FABP7 knockdown. UCP1 was induced in about 20% of cancer cells, and the effect was increased further in hypoxia. UCP1 depolarized mitochondrial membranes at the site of expression. UCP1 induction was associated with the increase in proton leak, glycolysis, and maximal respiration, mimicking the typical energy profile of beige adipocytes. Most importantly, UCP1 induction elevated cancer cell temperature associated with increased vulnerability to hypoxia and γ-irradiation.
conclusionsWe demonstrated that breast cancer cells can undergo thermogenesis through UCP1 induction. Disrupting FABP7-mediated fatty acid metabolism can unlock UCP1-mediated thermogenesis, potentially making it possible to develop therapies to target thermogenesis. Further study would be warranted to investigate the effect of rise in temperature of cancer cells on patients' outcomes and the relationship to other metabolic pathways.
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