ArticlePLoS genetics2013
Inflammation-mediated genetic and epigenetic alterations drive cancer development in the neighboring epithelium upon stromal abrogation of TGF-β signaling.
Article in PLoS genetics, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 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
48 citing papers in PubMed, 73 citations in OpenAlex.
- Oligomeric cystatin C supports the immunosuppressive activity of myeloid cells through interaction with inhibitory receptors.Signal transduction and targeted therapy · 2025Article
- Revisiting pulmonary fibrosis: inflammatory dynamics of the lipofibroblast-to-inflammatory lipofibroblast-to-activated myofibroblast reversible switch.Frontiers in immunology · 2025Review
- TGF-β signaling in health, disease, and therapeutics.Signal transduction and targeted therapy · 2024Review
- Skin aging from the perspective of dermal fibroblasts: the interplay between the adaptation to the extracellular matrix microenvironment and cell autonomous processes.Journal of cell communication and signaling · 2023Review
- TGFβ control of immune responses in cancer: a holistic immuno-oncology perspective.Nature reviews. Immunology · 2023Review
- Article
- Overcoming TGFβ-mediated immune evasion in cancer.Nature reviews. Cancer · 2022Review
- Can Pre-Treatment Inflammatory Parameters Predict the Probability of Sphincter-Preserving Surgery in Patients with Locally Advanced Low-Lying Rectal Cancer?Diagnostics (Basel, Switzerland) · 2021Article
- Dermal Fibroblast CCN1 Expression in Mice Recapitulates Human Skin Dermal Aging.The Journal of investigative dermatology · 2021Article
- Transforming Growth Factor-β: An Agent of Change in the Tumor Microenvironment.Frontiers in cell and developmental biology · 2021Review
- The Elevated Pre-Treatment C-Reactive Protein Predicts Poor Prognosis in Patients with Locally Advanced Rectal Cancer Treated with Neo-Adjuvant Radiochemotherapy.Diagnostics (Basel, Switzerland) · 2020Article
- Article
- Dualism of FGF and TGF-β Signaling in Heterogeneous Cancer-Associated Fibroblast Activation with ETV1 as a Critical Determinant.Cell reports · 2019Article
- Review
- Tumour-vasculature development via endothelial-to-mesenchymal transition after radiotherapy controls CD44v6Nature communications · 2018Article
- BMP7 Signaling inMolecular cancer research : MCR · 2018Article
- Genetics of metastasis: melanoma and other cancers.Clinical & experimental metastasis · 2018Review
- Major Challenges and Potential Microenvironment-Targeted Therapies in Glioblastoma.International journal of molecular sciences · 2017Review
- Mechanisms that drive inflammatory tumor microenvironment, tumor heterogeneity, and metastatic progression.Seminars in cancer biology · 2017Review
- Article
Corrections and comments
- Commented on by
Authors and funding
7 authors at 4 institutions in 1 country.
Funding
Abstract
Deletion of tumor suppressor genes in stromal fibroblasts induces epithelial cancer development, suggesting an important role of stroma in epithelial homoeostasis. However, the underlying mechanisms remain to be elucidated. Here we report that deletion of the gene encoding TGFβ receptor 2 (Tgfbr2) in the stromal fibroblasts (Tgfbr2(fspKO)) induces inflammation and significant DNA damage in the neighboring epithelia of the forestomach. This results in loss or down-regulation of cyclin-dependent kinase inhibitors p15, p16, and p21, which contribute to the development of invasive squamous cell carcinoma (SCC). Anti-inflammation treatment restored p21 expression, delayed tumorigenesis, and increased survival of Tgfbr2(fspKO) mice. Our data demonstrate for the first time that inflammation is a critical player in the epigenetic silencing of p21 in tumor progression. Examination of human esophageal SCC showed a down-regulation of TGFβ receptor 2 (TβRII) in the stromal fibroblasts, as well as increased inflammation, DNA damage, and loss or decreased p15/p16 expression. Our study suggests anti-inflammation may be a new therapeutic option in treating human SCCs with down-regulation of TβRII in the stroma.
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.