ArticleInternational journal of obesity (2005)2018
Leptin regulation of the p53-HIF1α/PKM2-aromatase axis in breast adipose stromal cells: a novel mechanism for the obesity-breast cancer link.
Article in International journal of obesity (2005), 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers, 3 of them syntheses that pooled it.
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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
41 citing papers in PubMed, 3 syntheses or guidelines pooled it, 64 citations in OpenAlex.
- Thermogenic Differentiation of Human Adipocyte Precursors in Culture: A Systematic Review.Cells · 2025Pooled it
- Association Between Triglyceride-Glucose Index and Breast Cancer: A Systematic Review and Meta-Analysis.Cancer reports (Hoboken, N.J.) · 2025Pooled it
- Advances in the Prevention and Treatment of Obesity-Driven Effects in Breast Cancers.Frontiers in oncology · 2022Pooled it
- Association of Body Fat and Risk of Breast Cancer in Postmenopausal Women With Normal Body Mass Index: A Secondary Analysis of a Randomized Clinical Trial and Observational Study.JAMA oncology · 2019Trial
- Targeting metabolic dysregulation in postmenopausal breast cancer: Synergistic effects of nutrition-based interventions and exercise on molecular and cellular pathways.Cancer cell international · 2026Review
- Exploring the Connection Between Ultra-Processed Foods and Breast Cancer: From Adiposity to Inflammation and Beyond.International journal of molecular sciences · 2026Review
- The evolving tumor-associated adipose tissue microenvironment in breast cancer: from cancer initiation to metastatic outgrowth.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Lactylation stabilizes DCBLD1 activating the pentose phosphate pathway to promote cervical cancer progression.Journal of experimental & clinical cancer research : CR · 2024Article
- Article
- Update on Adipose Tissue and Cancer.Endocrine reviews · 2023Article
- Article
- Molecular Mechanisms of Western Diet-Induced Obesity and Obesity-Related Carcinogenesis-A Narrative Review.Metabolites · 2023Review
- Review
- Obesity promotes breast epithelium DNA damage in women carrying a germline mutation inScience translational medicine · 2023Article
- Obesity and endocrine-related cancer: The important role of IGF-1.Frontiers in endocrinology · 2023Review
- Obesity as a Risk Factor for Breast Cancer-The Role of miRNA.International journal of molecular sciences · 2022Review
- The impact of obesity and adipokines on breast and gynecologic malignancies.Annals of the New York Academy of Sciences · 2022Review
- Escape from breast tumor dormancy: The convergence of obesity and menopause.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Differential Expression of HIF1A, EPAS1, and VEGF Genes in Benign and Malignant Ovarian Neoplasia.Cancers · 2022Article
- Review
Corrections and comments
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Authors and funding
11 authors at 4 institutions in 3 countries.
Funding
Abstract
BACKGROUND/
objectivesObesity (body mass index (BMI)⩾30 kg m SUBJECTS/
methodsHuman breast ASCs were used to characterize the p53-HIF1α/PKM2-aromatase axis in response to leptin. The effect of pharmacological or genetic modulation of protein kinase C (PKC), mitogen-activated protein kinase (MAPK), p53, Aha1, Hsp90, HIF1α and PKM2 on aromatase promoter activity, expression and enzyme activity was examined. Semiquantitative immunofluorescence and confocal imaging were used to assess ASC-specific protein expression in formalin-fixed paraffin-embedded tissue sections of breast of women and mammary tissue of mice following a low-fat (LF) or high-fat (HF) diet for 17 weeks.
resultsLeptin-mediated induction of aromatase was dependent on PKC/MAPK signaling and the suppression of p53. This, in turn, was associated with an increase in Aha1 protein expression, activation of Hsp90 and the stabilization of HIF1α and PKM2, known stimulators of aromatase expression. Consistent with these findings, ASC-specific immunoreactivity for p53 was inversely associated with BMI in breast tissue, while HIF1α, PKM2 and aromatase were positively correlated with BMI. In mice, HF feeding was associated with significantly lower p53 ASC-specific immunoreactivity compared with LF feeding, while immunoreactivity for HIF1α, PKM2 and aromatase were significantly higher.
conclusionsOverall, findings demonstrate a novel mechanism for the obesity-associated increase in aromatase in ASCs of the breast and support the study of lifestyle interventions, including weight management, which may reduce breast cancer risk via effects on this pathway.
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