ArticleOncogene2014
Interaction with colon cancer cells hyperactivates TGF-β signaling in cancer-associated fibroblasts.
Article in Oncogene, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 159 papers, 1 of them a synthesis that pooled it.
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Who cites it
159 citing papers in PubMed, 1 synthesis or guideline pooled it, 250 citations in OpenAlex.
- Effect of tumor microenvironment on pathogenesis of the head and neck squamous cell carcinoma: a systematic review.Molecular cancer · 2019Pooled it
- Disorganised stroma determined on pre-treatment breast cancer biopsies is associated with poor response to neoadjuvant chemotherapy: Results from the NEOZOTAC trial.Molecular oncology · 2015Trial
- Nitric Oxide in the Intestinal Stem Cell Niche: A Spatial Model of Nitrosative Stress and Clonal Evolution in Colitis-Associated Colorectal Cancer.Digestive diseases and sciences · 2026Review
- Label-Free Monitoring of Cancer-Associated Fibroblast Activation Using NAD(P)H Fluorescence Lifetime Imaging.Chembiochem : a European journal of chemical biology · 2026Article
- From inflammation to malignancy: the dynamic evolution of cancer-associated fibroblasts in IBD-CRC.Neoplasia (New York, N.Y.) · 2026Review
- Targeting fibroblast TXNDC5 resolves tumor desmoplasia and PD-1 resistance in colorectal cancer with mesenchymal traits.Nature communications · 2026Article
- DEC1 Deficiency Attenuates Breast Cancer-Induced Osteolytic Destruction by Suppression of Cancer-Associated Fibroblast Differentiation.Cancer medicine · 2026Article
- TGF-β Blockade With SB525334 Enhances B7-H3 CAR-γδT Cell Efficacy Against Glioblastoma.Journal of cellular and molecular medicine · 2026Article
- Prognostic significance of DNA ploidy, stroma fraction, and nucleotyping in stage IIIb colon cancer and their implications for adjuvant chemotherapy.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2026Article
- TGF-β in tumor development and progression: mechanisms and therapeutics.Molecular biomedicine · 2026Review
- Fruitful Interventions: A Narrative Review Addressing the Emerging Role of Antioxidant Fruits in Combating IBD-Driven Colorectal Cancer.Mini reviews in medicinal chemistry · 2026Review
- Article
- The function of metalloproteinases in pathophysiology of inflammatory bowel disease and colon cancer.Journal of leukocyte biology · 2025Review
- Crosstalk between cancer‑associated fibroblasts and inflammation in tumor microenvironment: A novel perspective in cancer therapy (Review).Oncology reports · 2025Review
- p53 Deficiency in Colon Cancer Cells Promotes Tumor Progression Through the Modulation of Meflin in Fibroblasts.Cancer science · 2025Article
- Targeting Redox Signaling Through Exosomal MicroRNA: Insights into Tumor Microenvironment and Precision Oncology.Antioxidants (Basel, Switzerland) · 2025Review
- Stromal Cell Subsets Show Model-Dependent Changes in Experimental Colitis and Affect Epithelial Tissue Repair and Immune Cell Activation.Inflammatory bowel diseases · 2025Article
- Quantitative Assessment of Collagen Architecture to Determine Role of Tumor Stroma During Vestibular Schwannoma Progression.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2025Article
- Enhancing fibroblast-epithelial cell communications: Serpine2 as a key molecule inFrontiers in immunology · 2025Article
- KRAS inhibitors may prevent colorectal cancer metachronous metastasis by suppressing TGF‑β mediated epithelial‑mesenchymal transition.Molecular medicine reports · 2025Article
99 more citing papers are in PubMed but not listed here.
Corrections and comments
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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
The interaction between epithelial cancer cells and cancer-associated fibroblasts (CAFs) has a major role in cancer progression and eventually in metastasis. In colorectal cancer (CRC), CAFs are present in high abundance, but their origin and functional interaction with epithelial tumor cells has not been elucidated. In this study we observed strong activation of the transforming growth factor-β (TGF-β)/Smad signaling pathway in CRC CAFs, accompanied by decreased signaling in epithelial tumor cells. We evaluated the TGF-β1 response and the expression of target genes including matrix metalloproteinases (MMPs) and plasminogen activator inhibitor (PAI)-1 of various epithelial CRC cell lines and primary CAFs in vitro. TGF-β1 stimulation caused high upregulation of MMPs, PAI-1 and TGF-β1 itself. Next we showed that incubation of CAFs with conditioned medium (CM) from epithelial cancer cells led to hyperactivation of the TGF-β signaling pathway, enhanced expression of target genes like PAI-1, and the expression of α-smooth muscle actin (α-SMA). We propose that the interaction of tumor cells with resident fibroblasts results in hyperactivated TGF-β1 signaling and subsequent transdifferentiation of the fibroblasts into α-SMA-positive CAFs. In turn this leads to cumulative production of TGF-β and proteinases within the tumor microenvironment, creating a cancer-promoting feedback loop.
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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.