ArticleThe Journal of biological chemistry2012
Leptin-induced epithelial-mesenchymal transition in breast cancer cells requires β-catenin activation via Akt/GSK3- and MTA1/Wnt1 protein-dependent pathways.
Article in The Journal of biological chemistry, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 121 papers, 3 of them syntheses that pooled it.
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Who cites it
121 citing papers in PubMed, 3 syntheses or guidelines pooled it, 193 citations in OpenAlex.
- A systematic review on leptin's role in defining cancer: special emphasis on immunomodulation, inflammation, and therapeutic interventions.Genes and immunity · 2025Pooled it
- Leptin signaling in breast cancer and its crosstalk with peroxisome proliferator-activated receptors α and γ.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2023Pooled it
- Prognostic and clinical significance of metastasis-associated gene 1 overexpression in solid cancers: A meta-analysis.Medicine · 2018Pooled it
- Leptin promotes endothelial dysfunction in chronic kidney disease by modulating the MTA1-mediated WNT/β-catenin pathway.Molecular and cellular biochemistry · 2020Trial
- Leptin Signaling at the Crossroads of Obesity, Immunity, and Cancer: Mechanistic Insights and Therapeutic Implications.Biomolecules & therapeutics · 2026Review
- Obesity-driven extracellular vesicle signaling in cancer: mechanistic insights and clinical implications.Oncogenesis · 2026Review
- Wnt ligands in breast cancer metastasis: unraveling their dual roles and therapeutic potential.Molecular biology reports · 2026Review
- Leptin Drives Breast Cancer Aggressiveness Acting Through the Activation of the NCOA1/STAT3 Pathway.Medical sciences (Basel, Switzerland) · 2026Article
- Research Progress on Signaling Pathways in Breast Cancer Bone Metastasis.Oncology research · 2026Review
- Quantitative impedance-based characterization of breast cancer cell migration and metastatic potential.Journal of biological engineering · 2025Article
- In-depth insight into tumor-infiltrating stromal cells linked to tertiary lymphoid structures and their prospective function in cancer immunotherapy.Experimental hematology & oncology · 2025Review
- Leptin-Upregulated Metastasis-Associated Protein 1 Promotes Vasculogenic Mimicry in Breast Cancer Cells.International journal of molecular sciences · 2025Article
- Micafungin exerts antitumor effect on breast cancer and osteosarcoma through preventing EMT in tumor cells in an USP7/AKT/GSK-3β pathway-dependent manner.Naunyn-Schmiedeberg's archives of pharmacology · 2024Article
- The Microbiome in the Obesity-Breast Cancer Axis: Diagnostic and Therapeutic Potential.Pathogens (Basel, Switzerland) · 2023Review
- Adipokines and epithelial-mesenchymal transition (EMT) in cancer.Molecular and cellular biochemistry · 2023Review
- Role of Leptin and Adiponectin in Carcinogenesis.Cancers · 2023Review
- Obesity and cancer: focus on leptin.Molecular biology reports · 2023Review
- Defining diurnal fluctuations in mouse choroid plexus and CSF at high molecular, spatial, and temporal resolution.Nature communications · 2023Article
- The activation of EP300 by F11R leads to EMT and acts as a prognostic factor in triple-negative breast cancers.The journal of pathology. Clinical research · 2023Article
- Anti-vimentin antibodies are associated with higher severity of Sjögren's disease.Clinical immunology (Orlando, Fla.) · 2023Article
61 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 4 institutions in 1 country.
Funding
Abstract
Perturbations in the adipocytokine profile, especially higher levels of leptin, are a major cause of breast tumor progression and metastasis; the underlying mechanisms, however, are not well understood. In particular, it remains elusive whether leptin is involved in epithelial-mesenchymal transition (EMT). Here, we provide molecular evidence that leptin induces breast cancer cells to undergo a transition from epithelial to spindle-like mesenchymal morphology. Investigating the downstream mediator(s) that may direct leptin-induced EMT, we found functional interactions between leptin, metastasis-associated protein 1 (MTA1), and Wnt1 signaling components. Leptin increases accumulation and nuclear translocation of β-catenin leading to increased promoter recruitment. Silencing of β-catenin or treatment with the small molecule inhibitor, ICG-001, inhibits leptin-induced EMT, invasion, and tumorsphere formation. Mechanistically, leptin stimulates phosphorylation of glycogen synthase kinase 3β (GSK3β) via Akt activation resulting in a substantial decrease in the formation of the GSK3β-LKB1-Axin complex that leads to increased accumulation of β-catenin. Leptin treatment also increases Wnt1 expression that contributes to GSK3β phosphorylation. Inhibition of Wnt1 abrogates leptin-stimulated GSK3β phosphorylation. We also discovered that leptin increases the expression of an important modifier of Wnt1 signaling, MTA1, which is integral to leptin-mediated regulation of the Wnt/β-catenin pathway as silencing of MTA1 inhibits leptin-induced Wnt1 expression, GSK3β phosphorylation, and β-catenin activation. Furthermore, analysis of leptin-treated breast tumors shows increased expression of Wnt1, pGSK3β, and vimentin along with higher nuclear accumulation of β-catenin and reduced E-cadherin expression providing in vivo evidence for a previously unrecognized cross-talk between leptin and MTA1/Wnt signaling in epithelial-mesenchymal transition of breast cancer cells.
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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.