ArticleMolecular oncology2013
Leptin increases HER2 protein levels through a STAT3-mediated up-regulation of Hsp90 in breast cancer cells.
Article in Molecular oncology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 56 papers, 1 of them a synthesis that pooled it.
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Who cites it
56 citing papers in PubMed, 1 synthesis or guideline pooled it, 78 citations in OpenAlex.
- Association of physical weight statuses defined by body mass index (BMI) with molecular subtypes of premenopausal breast cancer: a systematic review and meta-analysis.Breast cancer research and treatment · 2024Pooled it
- Review
- Complex Interplay Between Obesity and BRCA1/2-Associated Breast Cancer: An Overview.Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- 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
- Synergistic Activation of LEPR and ADRB2 Induced by Leptin Enhances Reactive Oxygen Specie Generation in Triple-Negative Breast Cancer Cells.Cancer research and treatment · 2025Article
- Obesity-Associated Breast Cancer: Analysis of Risk Factors and Current Clinical Evaluation.Advances in experimental medicine and biology · 2024Review
- The cellular composition of the tumor microenvironment is an important marker for predicting therapeutic efficacy in breast cancer.Frontiers in immunology · 2024Review
- Adipocyte-derived extracellular vesicles: bridging the communications between obesity and tumor microenvironment.Discover oncology · 2023Review
- Review
- Cancer-Associated Adipocytes and Breast Cancer: Intertwining in the Tumor Microenvironment and Challenges for Cancer Therapy.Cancers · 2023Review
- Breast Cancer Stem Cells: Signaling Pathways, Cellular Interactions, and Therapeutic Implications.Cancers · 2022Review
- The pleiotropic roles of adipocyte secretome in remodeling breast cancer.Journal of experimental & clinical cancer research : CR · 2022Review
- Prognostic significance of crown-like structures to trastuzumab response in patients with primary invasive HER2 + breast carcinoma.Scientific reports · 2022Article
- Computed tomography based analyses of body mass composition in HER2 positive metastatic breast cancer patients undergoing first line treatment with pertuzumab and trastuzumab.Scientific reports · 2022Article
- 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
- Prognostic impact of body mass index (BMI) in HER2+ breast cancer treated with anti-HER2 therapies: from preclinical rationale to clinical implications.Therapeutic advances in medical oncology · 2022Review
- Impact of native and external factors on exosome release: understanding reactive exosome secretion and its biogenesis.Molecular biology reports · 2021Review
- Hyperleptinemia in obese state renders luminal breast cancers refractory to tamoxifen by coordinating a crosstalk between Med1, miR205 and ErbB.NPJ breast cancer · 2021Article
- Association between clinicopathological features of breast cancer with adipocytokine levels and oxidative stress markers before and after chemotherapy.Biomedical reports · 2021Article
- The Adipokine Component in the Molecular Regulation of Cancer Cell Survival, Proliferation and Metastasis.Pathology oncology research : POR · 2021Review
Corrections and comments
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Authors and funding
11 authors at 3 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Obesity condition confers risks to breast cancer development and progression, and several reports indicate that the adipokine leptin, whose synthesis and plasma levels increase with obesity, might play an important role in modulating breast cancer cell phenotype. Functional crosstalk occurring between leptin and different signaling molecules contribute to breast carcinogenesis. In this study, we show, in different human breast cancer cell lines, that leptin enhanced the expression of a chaperone protein Hsp90 resulting in increased HER2 protein levels. Silencing of Hsp90 gene expression by RNA interference abrogated leptin-mediated HER2 up-regulation. Leptin effects were dependent on JAK2/STAT3 activation, since inhibition of this signaling cascade by AG490 or ectopic expression of a STAT3 dominant negative abrogated leptin-induced HER2 and Hsp90 expressions. Functional experiments showed that leptin treatment significantly up-regulated human Hsp90 promoter activity. This occurred through an enhanced STAT3 transcription factor binding to its specific responsive element located in the Hsp90 promoter region as revealed by electrophoretic mobility shift assay and chromatin immunoprecipitation assay. Analysis of HER2, Akt and MAPK phosphorylation levels revealed that leptin treatment amplified the responsiveness of breast cancer cells to growth factor stimulation. Furthermore, we found that long-term leptin exposure reduced sensitivity of breast cancer cells to the antiestrogen tamoxifen. In the same experimental conditions, the combined treatment of tamoxifen with the Hsp90 inhibitor 17-AAG completely abrogated leptin-induced anchorage-independent breast cancer cell growth. In conclusion, our results highlight, for the first time, the ability of the adipocyte-secreted factor leptin to modulate Hsp90/HER2 expressions in breast cancer cells providing novel insights into the molecular mechanism linking obesity to breast cancer growth and progression.
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