ArticlePloS one2015
TGF-β Negatively Regulates CXCL1 Chemokine Expression in Mammary Fibroblasts through Enhancement of Smad2/3 and Suppression of HGF/c-Met Signaling Mechanisms.
Article in PloS one, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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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.
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Who cites it
23 citing papers in PubMed, 29 citations in OpenAlex.
- TGF-β1 inhibits CXCL1/CXCR2 signaling pathway to alleviate neuropathic pain in a spinal nerve ligation rat model.Journal of molecular histology · 2026Article
- C-X-C motif chemokine ligand 1 derived from oral squamous cell carcinoma promotes cancer-associated fibroblast differentiation and tumor growth.Molecular biomedicine · 2025Article
- TGFβ1 induces CXCL1 to promote stemness features in lung cancer.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Enamel Matrix Derivative Suppresses Chemokine Expression in Oral Epithelial Cells.International journal of molecular sciences · 2023Article
- Overview of the therapeutic strategies for ER positive breast cancer.Biochemical pharmacology · 2023Review
- Involvement in Tumorigenesis and Clinical Significance of CXCL1 in Reproductive Cancers: Breast Cancer, Cervical Cancer, Endometrial Cancer, Ovarian Cancer and Prostate Cancer.International journal of molecular sciences · 2023Review
- ADAMTS1 induces epithelial-mesenchymal transition pathway in non-small cell lung cancer by regulating TGF-β.Aging · 2023Article
- HSP90/IKK-rich small extracellular vesicles activate pro-angiogenic melanoma-associated fibroblasts via the NF-κB/CXCL1 axis.Cancer science · 2022Article
- Family with sequence similarity 46 member a confers chemo-resistance to ovarian carcinoma via TGF-β/Smad2 signaling.Bioengineered · 2022Article
- Review
- Visfatin Enhances Breast Cancer Progression through CXCL1 Induction in Tumor-Associated Macrophages.Cancers · 2020Article
- C/EBPɑ is crucial determinant of epithelial maintenance by preventing epithelial-to-mesenchymal transition.Nature communications · 2020Article
- Mesenchymal Stem Cells from Chronic Pancreatitis Patients Show Comparable Potency Compared to Cells from Healthy Donors.Stem cells translational medicine · 2019Article
- Cancer-cell-secreted CXCL11 promoted CD8Journal for immunotherapy of cancer · 2019Article
- Semaphorin4D Inhibition Improves Response to Immune-Checkpoint Blockade via Attenuation of MDSC Recruitment and Function.Cancer immunology research · 2019Article
- Protein Glycosylation and Tumor Microenvironment Alterations Driving Cancer Hallmarks.Frontiers in oncology · 2019Review
- CXCL1 Derived from Mammary Fibroblasts Promotes Progression of Mammary Lesions to Invasive Carcinoma through CXCR2 Dependent Mechanisms.Journal of mammary gland biology and neoplasia · 2018Article
- Cancer Associated Fibroblasts: Naughty Neighbors That Drive Ovarian Cancer Progression.Cancers · 2018Review
- Continuous Delivery of Neutralizing Antibodies Elevate CCL2 Levels in Mice Bearing MCF10CA1d Breast Tumor Xenografts.Translational oncology · 2017Article
- Cancer-associated fibroblasts enhance metastatic potential of lung cancer cells through IL-6/STAT3 signaling pathway.Oncotarget · 2017Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Fibroblasts are major cellular components of the breast cancer stroma, and influence the growth, survival and invasion of epithelial cells. Compared to normal tissue fibroblasts, carcinoma associated fibroblasts (CAFs) show increased expression of numerous soluble factors including growth factors and cytokines. However, the mechanisms regulating expression of these factors remain poorly understood. Recent studies have shown that breast CAFs overexpress the chemokine CXCL1, a key regulator of tumor invasion and chemo-resistance. Increased expression of CXCL1 in CAFs correlated with poor patient prognosis, and was associated with decreased expression of TGF-β signaling components. The goal of these studies was to understand the role of TGF-β in regulating CXCL1 expression in CAFs, using cell culture and biochemical approaches. We found that TGF-β treatment decreased CXCL1 expression in CAFs, through Smad2/3 dependent mechanisms. Chromatin immunoprecipitation and site-directed mutagenesis assays revealed two new binding sites in the CXCL1 promoter important for Smad2/3 modulation of CXCL1 expression. Smad2/3 proteins also negatively regulated expression of Hepatocyte Growth Factor (HGF), which was found to positively regulate CXCL1 expression in CAFs through c-Met receptor dependent mechanisms. HGF/c-Met signaling in CAFs was required for activity of NF-κB, a transcriptional activator of CXCL1 expression. These studies indicate that TGF-β negatively regulates CXCL1 expression in CAFs through Smad2/3 binding to the promoter, and through suppression of HGF/c-Met autocrine signaling. These studies reveal novel insight into how TGF-β and HGF, key tumor promoting factors modulate CXCL1 chemokine expression in CAFs.
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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.