ArticlePloS one2014
Caffeine mediates sustained inactivation of breast cancer-associated myofibroblasts via up-regulation of tumor suppressor genes.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
What it found
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Who cites it
25 citing papers in PubMed, 38 citations in OpenAlex.
- Phytochemical Characterization and Antioxidant/Antitumoral Potential of Coffee Silverskin: Comparative Insights with Green and Roasted Coffee.Foods (Basel, Switzerland) · 2026Article
- Emerging agents that target signaling pathways in cancer fibroblast cells (Review).International journal of oncology · 2026Review
- Association Between Coffee and Caffeine Intake and Risk of Breast Cancer: A Systematic Review and Meta-Analysis of Cohort Studies.Health science reports · 2026Review
- Recombinant Human Decorin Normalizes the Active Features of Breast Cancer-Associated Fibroblasts.Cells · 2026Article
- Upregulation of Caveolin-1 in breast cancer and its potential value in distinguishing TNBC from non-TNBC: an immunohistochemical study.Frontiers in oncology · 2026Article
- Review
- Unlocking the crucial role of cancer-associated fibroblasts in tumor metastasis: Mechanisms and therapeutic prospects.Journal of advanced research · 2025Review
- Caveolin-1: an ambiguous entity in breast cancer.Molecular cancer · 2025Review
- Coffee consumption, cancer, and healthy aging: epidemiological evidence and underlying mechanisms.GeroScience · 2025Review
- Bioactive compounds in coffee and their role in lowering the risk of major public health consequences: A review.Food science & nutrition · 2024Review
- Silver and Copper Complexes with Ibuprofen and Caffeine-Preparation and Evaluation of Their Selected Biological Effects.Molecules (Basel, Switzerland) · 2024Article
- Crosstalk and plasticity driving between cancer-associated fibroblasts and tumor microenvironment: significance of breast cancer metastasis.Journal of translational medicine · 2023Review
- Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-β/Smad pathway.Acta biochimica et biophysica Sinica · 2022Article
- Targeting transforming growth factor-β signalling for cancer prevention and intervention: Recent advances in developing small molecules of natural origin.Clinical and translational medicine · 2022Review
- Consumption of Food Components of the Mediterranean Diet Decreases the Risk of Breast Cancer in the Makkah Region, Saudi Arabia: A Case-Control Study.Frontiers in nutrition · 2022Article
- Coffee consumption and breast cancer risk: a narrative review in the general population and in different subtypes of breast cancer.European journal of nutrition · 2021Review
- Caveolin-1: a multifaceted driver of breast cancer progression and its application in clinical treatment.OncoTargets and therapy · 2019Review
- Expression of Genes for Methylxanthine Pathway-Associated Enzymes Accompanied by Sex Steroid Receptor Status Impacts Breast Carcinoma Progression.Hormones & cancer · 2017Article
- Caffeine induces sustained apoptosis of human gastric cancer cells by activating the caspase‑9/caspase‑3 signalling pathway.Molecular medicine reports · 2017Article
- The inflammatory/cancer-related IL-6/STAT3/NF-κB positive feedback loop includes AUF1 and maintains the active state of breast myofibroblasts.Oncotarget · 2016Article
Corrections and comments
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Authors and funding
2 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundActive cancer-associated fibroblasts (CAFs) or myofibroblasts play important roles not only in the development and progression of breast carcinomas, but also in their prognosis and treatment. Therefore, targeting these cells through suppressing their supportive procarcinogenic paracrine effects is mandatory for improving the current therapies that are mainly targeting tumor cells. To this end, we investigated the effect of the natural and pharmacologically safe molecule, caffeine, on CAF cells and their various procarcinogenic effects. METHODOLOGY/PRINCIPAL
findingsWe have shown here that caffeine up-regulates the tumor suppressor proteins p16, p21, p53 and Cav-1, and reduces the expression/secretion of various cytokines (IL-6, TGF-β, SDF-1 and MMP-2), and down-regulates α-SMA. Furthermore, caffeine suppressed the migratory/invasiveness abilities of CAF cells through PTEN-dependent Akt/Erk1/2 inactivation. Moreover, caffeine reduced the paracrine pro-invasion/-migration effects of CAF cells on breast cancer cells. These results indicate that caffeine can inactivate breast stromal myofibroblasts. This has been confirmed by showing that caffeine also suppresses the paracrine pro-angiogenic effect of CAF cells through down-regulating HIF-1αand its downstream effector VEGF-A. Interestingly, these effects were sustained in absence of caffeine. CONCLUSION/SIGNIFICANCE: The present findings provide a proof of principle that breast cancer myofibroblasts can be inactivated, and thereby caffeine may provide a safe and effective prevention against breast tumor growth/recurrence through inhibition of the procarcinogenic effects of active stromal fibroblasts.
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