ArticleCell communication and signaling : CCS2018
Adipocyte-derived IL-6 and leptin promote breast Cancer metastasis via upregulation of Lysyl Hydroxylase-2 expression.
Article in Cell communication and signaling : CCS, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 101 papers, 2 of them syntheses that pooled it.
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Who cites it
101 citing papers in PubMed, 2 syntheses or guidelines pooled it, 123 citations in OpenAlex.
- Targeting Ferroptosis as the Achilles' Heel of Breast Cancer: Mechanisms and Therapeutic Opportunities from a Comprehensive Systematic Review.International journal of molecular sciences · 2025Pooled it
- Importance of circulating adipocytokines in multiple myeloma: a systematic review and meta-analysis based on case-control studies.BMC endocrine disorders · 2022Pooled it
- Extracellular Matrix Remodeling in Tumors: Forces Beyond Fibroblasts.Cancer research · 2026Article
- Obesity-driven adipokine signaling in breast cancer: mechanistic insights, therapeutic challenges, and opportunities for precision oncology.Journal of pathology and translational medicine · 2026Article
- IL-6/STAT3 signaling pathway-mediated apoptosis induced by medical ozone water in liver cancer: A mechanistic study.Biomedical reports · 2026Article
- Lipid Metabolism, Lipogenesis, and Resistance to Third Generation EGFR-TKIs.Journal of clinical laboratory analysis · 2026Review
- Leptin Signaling at the Crossroads of Obesity, Immunity, and Cancer: Mechanistic Insights and Therapeutic Implications.Biomolecules & therapeutics · 2026Review
- TIA1 depletion enhances CLSTN1 exon 11 inclusion to facilitate Epithelial-to-Mesenchymal transition and breast cancer metastasis.Oncogene · 2026Article
- Collagen remodeling in breast cancer progression: from molecular mechanisms to diagnostic and therapeutic opportunities.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Intratumoral and Peritumoral Fat CT‑Based Radiomics for Predicting Recurrence Risk in Non-Muscle-Invasive Bladder Cancer: A Two-Center Study.Annals of surgical oncology · 2026Article
- Metabolic crosstalk among cancer-associated fibroblasts, adipocytes and immune cells as an immunosuppressive tumor microenvironment driver.Experimental & molecular medicine · 2026Review
- Leptin Drives Breast Cancer Aggressiveness Acting Through the Activation of the NCOA1/STAT3 Pathway.Medical sciences (Basel, Switzerland) · 2026Article
- The mechanisms and therapeutic advances of interactions between breast cancer and cardiovascular diseases.Frontiers in pharmacology · 2026Review
- Uncovering GSTK1 and PTGER3 as biomarkers for breast cancer prognosis through comprehensive analyses.Discover oncology · 2025Article
- Rhapontigenin Suppresses Leptin-Induced Vasculogenic Mimicry by Inhibiting STAT3-Aquaporin-1 Axis in TNBC Cells.Biomedicines · 2025Article
- Fusobacterium nucleatum-reprogrammed adipocytes promote tumor cisplatin resistance through the CCL2-CCR2 axis in the necrotic metastatic neck nodes of head and neck carcinoma.Cell communication and signaling : CCS · 2025Article
- Necrotic and apoptotic adipocytes in the hypoxic tumor microenvironment supply triglycerides to induce cisplatin resistance in the metastatic lymph nodes of head and neck carcinoma.Cell death & disease · 2025Article
- Is Adipose Tissue Inflammation the Culprit of Obesity-Associated Comorbidities?Obesity reviews : an official journal of the International Association for the Study of Obesity · 2025Review
- The value of C-TIRADS combined with multidimensional indicators in the diagnosis of papillary thyroid carcinoma.Gland surgery · 2025Article
- CAA-derived IL-6 promoted the PD-L1 expression of breast cancer via STAT3/miR-497a-5p signaling.Journal of cancer research and clinical oncology · 2025Article
41 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundAdipocytes make up the major component of breast tissue, accounting for 90% of stromal tissue. Thus, the crosstalk between adipocytes and breast cancer cells may play a critical role in cancer progression. Adipocyte-breast cancer interactions have been considered important for the promotion of breast cancer metastasis. However, the specific mechanisms underlying these interactions are unclear. In this study, we investigated the mechanisms of adipocyte-mediated breast cancer metastasis.
methodsBreast cancer cells were cocultured with mature adipocytes for migration and 3D matrix invasion assays. Next, lentivirus-mediated loss-of-function experiments were used to explore the function of lysyl hydroxylase (PLOD2) in breast cancer migration and adipocyte-dependent migration of breast cancer cells. The role of PLOD2 in breast cancer metastasis was further confirmed using orthotopic mammary fat pad xenografts in vivo. Clinical samples were used to confirm that PLOD2 expression is increased in tumor tissue and is associated with poor prognosis of breast cancer patients. Cells were treated with cytokines and pharmacological inhibitors in order to verify which adipokines were responsible for activation of PLOD2 expression and which signaling pathways were activated in vitro.
resultsGene expression profiling and Western blotting analyses revealed that PLOD2 was upregulated in breast cancer cells following coculture with adipocytes; this process was accompanied by enhanced breast cancer cell migration and invasion. Loss-of-function studies indicated that PLOD2 knockdown suppressed cell migration and disrupted the formation of actin stress fibers in breast cancer cells and abrogated the migration induced by following coculture with adipocytes. Moreover, experiments performed in orthotopic mammary fat pad xenografts showed that PLOD2 knockdown could reduce metastasis to the lung and liver. Further, high PLOD2 expression correlated with poor prognosis of breast cancer patients. Mechanistically, adipocyte-derived interleukin-6 (IL-6) and leptin may facilitate PLOD2 upregulation in breast cancer cells and promote breast cancer metastasis in tail vein metastasis assays. Further investigation revealed that adipocyte-derived IL-6 and leptin promoted PLOD2 expression through activation of the JAK/STAT3 and PI3K/AKT signaling pathways.
conclusionsOur study reveals that adipocyte-derived IL-6 and leptin promote PLOD2 expression by activating the JAK/STAT3 and PI3K/AKT signaling pathways, thus promoting breast cancer metastasis.
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