ArticleBiomolecules2020
Leptin Signaling Contributes to Aromatase Inhibitor Resistant Breast Cancer Cell Growth and Activation of Macrophages.
Article in Biomolecules, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 42 citations in OpenAlex.
- Adipocyte-derived estrogen signaling influences TROP2 expression in ERα-positive breast cancer.Frontiers in endocrinology · 2026Article
- Adipocyte‑derived extracellular vesicles sustain mitochondrial metabolism in breast cancer cells: New insights into the cross‑talk between cancer cells and the tumor microenvironment.International journal of oncology · 2025Article
- Machine learning analysis reveals tumor heterogeneity and stromal-immune niches in breast cancer.NPJ digital medicine · 2025Article
- Adipocyte/Tumor cell crosstalk via IGF-1/TXNIP axis promotes malignancy and endocrine resistance in breast cancer.Cell communication and signaling : CCS · 2025Article
- Decoding breast cancer treatment resistance through genetic, epigenetic, and immune-regulatory mechanisms: from molecular insights to translational perspectives.Cancer drug resistance (Alhambra, Calif.) · 2025Review
- Implications of obesity and insulin resistance for the treatment of oestrogen receptor-positive breast cancer.British journal of cancer · 2024Review
- Adipose Tissues Have Been Overlooked as Players in Prostate Cancer Progression.International journal of molecular sciences · 2024Review
- Chemotherapy-elicited extracellular vesicle CXCL1 from dying cells promotes triple-negative breast cancer metastasis by activating TAM/PD-L1 signaling.Journal of experimental & clinical cancer research : CR · 2024Article
- Modeling of Mouse Experiments Suggests that Optimal Anti-Hormonal Treatment for Breast Cancer is Diet-Dependent.Bulletin of mathematical biology · 2024Article
- Towards Understanding the Development of Breast Cancer: The Role of RhoJ in the Obesity Microenvironment.Cells · 2024Article
- Exploring the multifaceted role of obesity in breast cancer progression.Frontiers in cell and developmental biology · 2024Review
- Soloxolone Methyl Reduces the Stimulatory Effect of Leptin on the Aggressive Phenotype of Murine Neuro2a Neuroblastoma Cells via the MAPK/ERK1/2 Pathway.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Leptin: A Heavyweight Player in Obesity-Related Cancers.Biomolecules · 2023Review
- The Pro-Tumorigenic Role of Chemotherapy-Induced Extracellular HSP70 from Breast Cancer Cells via Intratumoral Macrophages.Cancers · 2023Article
- Understanding the mechanisms underlying obesity in remodeling the breast tumor immune microenvironment: from the perspective of inflammation.Cancer biology & medicine · 2023Review
- The role of the tumor microenvironment in endocrine therapy resistance in hormone receptor-positive breast cancer.Frontiers in endocrinology · 2023Review
- Proteomic Profiling of Extracellular Vesicles Released by Leptin-Treated Breast Cancer Cells: A Potential Role in Cancer Metabolism.International journal of molecular sciences · 2022Article
- The pleiotropic roles of adipocyte secretome in remodeling breast cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Obesity and endocrine therapy resistance in breast cancer: Mechanistic insights and perspectives.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2022Review
- Leptin and Beyond: Actors in Cancer.Biomolecules · 2021Article
Corrections and comments
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Authors and funding
15 authors at 3 institutions in 2 countries.
Funding
Abstract
Obesity represents a risk factor for breast cancer development and therapy resistance, but the molecular players underling these links are unclear. Here, we identify a role for the obesity-cytokine leptin in sustaining aromatase inhibitor (AI) resistant growth and progression in breast cancer. Using as experimental models MCF-7 breast cancer cells surviving long-term treatment with the AI anastrozole (AnaR) and Ana-sensitive counterparts, we found that AnaR cells expressed higher levels of leptin and its receptors (ObR) along with a constitutive activation of downstream effectors. Accordingly, leptin signaling inhibition reduced only AnaR cell growth and motility, highlighting the existence of an autocrine loop in mechanisms governing drug-resistant phenotypes. In agreement with ObR overexpression, increasing doses of leptin were able to stimulate to a greater extent growth and migration in AnaR than sensitive cells. Moreover, leptin contributed to enhanced crosstalk between AnaR cells and macrophages within the tumor microenvironment. Indeed, AnaR, through leptin secretion, modulated macrophage profiles and increased macrophage motility through CXCR4 signaling, as evidenced by RNA-sequencing, real-time PCR, and immunoblotting. Reciprocally, activated macrophages increased AnaR cell growth and motility in coculture systems. In conclusion, acquired AI resistance is accompanied by the development of a leptin-driven phenotype, highlighting the potential clinical benefit of targeting this cytokine network in hormone-resistant breast cancers, especially in obese women.
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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.