ArticleOncogene2019
Elevated leptin disrupts epithelial polarity and promotes premalignant alterations in the mammary gland.
Article in Oncogene, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
34 citing papers in PubMed, 46 citations in OpenAlex.
- Characterization of intestinal immune responses in generalized human and murine lipodystrophy.The Journal of clinical investigation · 2026Article
- Leptin Therapy Improves Metabolic Dysfunction in Immune Checkpoint Inhibitor-induced Lipodystrophy.JCEM case reports · 2026Article
- Control of epithelial homeostasis by apical polarity: it takes a network.Biochemical Society transactions · 2025Article
- Longitudinal changes in body composition during palliative systemic chemotherapy and survival outcomes in metastatic colorectal cancer.World journal of gastrointestinal oncology · 2025Article
- Obesity increases DNA damage in the breast epithelium.Breast cancer research : BCR · 2025Article
- The epithelial polarity axis controls the resting membrane potential and Cl- co-transport in breast glandular structures.Journal of cell science · 2024Article
- Nonmetastatic Axillary Lymph Nodes Have Distinct Morphology and Immunophenotype in Obese Patients with Breast Cancer at Risk for Metastasis.The American journal of pathology · 2024Article
- The microbiome: a link between obesity and breast cancer risk.Frontiers in microbiomes · 2024Review
- Reversion of breast epithelial polarity alterations caused by obesity.NPJ breast cancer · 2023Article
- Obesity and cancer stem cells: Roles in cancer initiation, progression and therapy resistance.World journal of stem cells · 2023Review
- Annexin A1 is a polarity cue that directs mitotic spindle orientation during mammalian epithelial morphogenesis.Nature communications · 2023Article
- Over-expression of miR-183-5p or miR-492 triggers invasion and proliferation and loss of polarity in non-neoplastic breast epithelium.Scientific reports · 2022Article
- The impact of obesity and adipokines on breast and gynecologic malignancies.Annals of the New York Academy of Sciences · 2022Review
- Berberine inhibits carcinogenesis through antagonizing the ATX-LPA-LPAR2-p38-leptin axis in a mouse hepatoma model.Molecular therapy oncolytics · 2022Article
- The obesity-breast cancer link: a multidisciplinary perspective.Cancer metastasis reviews · 2022Review
- Role of Diet in Stem and Cancer Stem Cells.International journal of molecular sciences · 2022Review
- Chronic Leptin Treatment Induces Epithelial-Mesenchymal Transition in MCF10A Mammary Epithelial Cells.Journal of mammary gland biology and neoplasia · 2022Article
- Nutritional Regulation of Mammary Tumor Microenvironment.Frontiers in cell and developmental biology · 2022Review
- Emerging Cnidarian Models for the Study of Epithelial Polarity.Frontiers in cell and developmental biology · 2022Review
- Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 1 country.
Funding
Abstract
Obesity is a highly prevalent and modifiable breast cancer risk factor. While the role of obesity in fueling breast cancer progression is well established, the mechanisms linking obesity to breast cancer initiation are poorly understood. A hallmark of breast cancer initiation is the disruption of apical polarity in mammary glands. Here we show that mice with diet-induced obesity display mislocalization of Par3, a regulator of cellular junctional complexes defining mammary epithelial polarity. We found that epithelial polarity loss also occurs in a 3D coculture system that combines acini with human mammary adipose tissue, and establish that a paracrine effect of the tissue adipokine leptin causes loss of polarity by overactivation of the PI3K/Akt pathway. Leptin sensitizes non-neoplastic cells to proliferative stimuli, causes mitotic spindle misalignment, and expands the pool of cells with stem/progenitor characteristics, which are early steps for cancer initiation. We also found that normal breast tissue samples with high leptin/adiponectin transcript ratio characteristic of obesity have an altered distribution of apical polarity markers. This effect is associated with increased epithelial cell layers. Our results provide a molecular basis for early alterations in epithelial architecture during obesity-mediated cancer initiation.
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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.