ArticleOncotarget2017
Lactate-activated macrophages induced aerobic glycolysis and epithelial-mesenchymal transition in breast cancer by regulation of CCL5-CCR5 axis: a positive metabolic feedback loop.
Article in Oncotarget, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 78 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
78 citing papers in PubMed, 90 citations in OpenAlex.
- Unveiling CCL5: the master regulator of breast cancer progression and immune evasion.Breast cancer research : BCR · 2026Review
- Metformin's disruption of gluconeogenesis in type 2 diabetes impairments of the cori and alanine cycles as hidden drivers of metabolic waste accumulation, NF-κBHIF-1α-mediated low-grade inflammation, and multisystem dysfunction.Problemy endokrinologii · 2026Review
- Immunity and Beyond: Emerging Roles of Monocytes and Macrophages in Cancer.Advances in experimental medicine and biology · 2026Review
- Lactate, a Spearhead of Cancer Aggressiveness: Metabolic Reprogramming, Immune Suppression, and Metastatic Progression.Medical principles and practice : international journal of the Kuwait University, Health Science Centre · 2026Review
- Advancements in research on the role of the key glycolytic enzyme hexokinase 2 in the regulation of tumor immune evasion (Review).Oncology letters · 2025Review
- Smart biomimetic "nano-med-fireman" blocking inflammation and lactate metabolism crosstalk for normalized spatiotemporal photo-immunotherapy.Bioactive materials · 2025Article
- Tumor-Associated Macrophage in Breast Tumor Microenvironment.International journal of molecular sciences · 2025Review
- Review
- Lactate metabolism and lactylation in breast cancer: mechanisms and implications.Cancer metastasis reviews · 2025Review
- Tumor Microenvironment Lactate: Is It a Cancer Progression Marker, Immunosuppressant, and Therapeutic Target?Molecules (Basel, Switzerland) · 2025Review
- The General Principle of the Warburg Effect as a Possible Approach for Cancer Immunotherapy: The Regulatory Effect of Plant Extracts Could Change the Game.Molecules (Basel, Switzerland) · 2025Review
- The lactylation-macrophage interplay: implications for gastrointestinal disease therapeutics.Frontiers in immunology · 2025Review
- Chemokines: humble yet mighty players in the tumour microenvironment.Frontiers in immunology · 2025Review
- Increased levels of versican and insulin-like growth factor 1 in peritumoral mammary adipose tissue are related to aggressiveness in estrogen receptor-positive breast cancer.Molecular medicine (Cambridge, Mass.) · 2024Article
- FGFR‑related phenotypic and functional profile of CAFs in prognostication of breast cancer (Review).International journal of oncology · 2024Review
- From monocyte-derived macrophages to resident macrophages-how metabolism leads their way in cancer.Molecular oncology · 2024Review
- Targeting tumor‑associated macrophages: Critical players in tumor progression and therapeutic strategies (Review).International journal of oncology · 2024Review
- A new perspective on the therapeutic potential of tumor metastasis: targeting the metabolic interactions between TAMs and tumor cells.International journal of biological sciences · 2024Review
- Targeting the chemokines in acute graft-versus-host disease.Frontiers in immunology · 2024Review
- Polylactide Degradation Activates Immune Cells by Metabolic Reprogramming.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
18 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Aberrant energy metabolism is critical for cancer progression. Tumor-associated macrophages (TAMs) can stimulate tumor angiogenesis and enhance cancer metastasis; however, the metabolic interaction between cancer cells and macrophages characterized by lactate shuttles remains unclear. Here, we showed that lactate activated human macrophages to a TAM-like phenotype and stimulated the secretion of CCL5 by activation of Notch signaling in macrophages. Reciprocally, CCL5 increased cell migration, induced cancer cell EMT, and promoted aerobic glycolysis in breast cancer cells, suggesting a positive metabolic feedback loop in the co-culture system. Inhibition of CCR5, the cognate receptor of CCL5, or neutralization of CCL5, broke the metabolic loop and decreased cancer cell migration and EMT. Inhibition of aerobic glycolysis significantly reduced breast cancer cell EMT, indicated that aerobic glycolysis was necessary for the invasive phenotype of cancer cells. We further showed that TGF-β signaling regulated the expression of CCR5 in the co-culture system, and CCL5 induced glycolysis by mediation of AMPK signaling. The expression of CCL5-CCR5 axis was highly associated with macrophage infiltration, TGF-β and p-AMPK in clinical samples. CCL5-CCR5 axis promoted breast cancer metastasis
Indexed as
Identifiers
What OpenQuestion holds
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.