ArticleCancer letters2021
Normalizing glucose levels reconfigures the mammary tumor immune and metabolic microenvironment and decreases metastatic seeding.
Article in Cancer letters, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 20 citations in OpenAlex.
- Neoadjuvant metformin on clinical and pathological response in non-diabetic patients with non-metastatic breast cancer: an updated systematic review and meta-analysis.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Review
- Metabolic Reprogramming-Driven Cardiovascular Immune Damage: From Glyco-Lipotoxicity and Epigenetic Memory to Multidimensional Cross-Organ Communication Networks.International journal of molecular sciences · 2026Review
- Collagen dynamics in the breast cancer tumor microenvironment and therapeutic perspectives.Discover oncology · 2025Review
- Immunometabolism: crosstalk with tumor metabolism and implications for cancer immunotherapy.Molecular cancer · 2025Review
- O‑GlcNAcylation as an emerging molecular target for cholangiocarcinoma therapy (Review).Oncology reports · 2025Review
- PET Imaging of Diabetes-Induced Alterations in Metabolism and Immune Activation.Molecular imaging and biology · 2025Article
- Short-term consumption of the modified standard American diet perturbed the metabolic balance and altered DNA damage in MMTV-PyMT transgenic mice.Breast cancer research : BCR · 2025Article
- Cancer immunometabolism: advent, challenges, and perspective.Molecular cancer · 2024Review
- Diabetes-associated breast cancer is molecularly distinct and shows a DNA damage repair deficiency.JCI insight · 2023Article
- Development and validation of a nomogram to predict occult cervical metastasis in early oral squamous cell carcinoma.Annals of translational medicine · 2023Article
- Breast cancer microenvironment and obesity: challenges for therapy.Cancer metastasis reviews · 2022Review
- A precision medicine approach to metabolic therapy for breast cancer in mice.Communications biology · 2022Article
- Article
- Insulin and cancer: a tangled web.The Biochemical journal · 2022Review
- Effect of naturally derived surgical hemostatic materials on the proliferation of A549 human lung adenocarcinoma cells.Materials today. Bio · 2022Article
- O-GlcNAcylation regulation of cellular signaling in cancer.Cellular signalling · 2022Review
Corrections and comments
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Authors and funding
11 authors at 1 institution in 1 country.
Funding
Abstract
Obesity and diabetes cumulatively create a distinct systemic metabolic pathophysiological syndrome that predisposes patients to several diseases including breast cancer. Moreover, diabetic and obese women with breast cancer show a significant increase in mortality compared to non-obese and/or non-diabetic women. We hypothesized that these metabolic conditions incite an aggressive tumor phenotype by way of impacting tumor cell-autonomous and tumor cell non-autonomous events. In this study, we established a type 2 diabetic mouse model of triple-negative mammary carcinoma and investigated the effect of a glucose lowering therapy, metformin, on the overall tumor characteristics and immune/metabolic microenvironment. Diabetic mice exhibited larger mammary tumors that had increased adiposity with high levels of O-GlcNAc protein post-translational modification. These tumors also presented with a distinct stromal profile characterized by altered collagen architecture, increased infiltration by tumor-permissive M2 macrophages, and early metastatic seeding compared to non-diabetic/lean mice. Metformin treatment of the diabetic/obese mice effectively normalized glucose levels, reconfigured the mammary tumor milieu, and decreased metastatic seeding. Our results highlight the impact of two metabolic complications of obesity and diabetes on tumor cell attributes and showcase metformin's ability to revert tumor cell and stromal changes induced by an obese and diabetic host environment.
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