ArticleGastroenterology2022
SMAD4 Suppresses Colitis-associated Carcinoma Through Inhibition of CCL20/CCR6-mediated Inflammation.
Article in Gastroenterology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 44 citations in OpenAlex.
- TNF-α-responsive YAP1 promotes CCL20 expression in colorectal inflammation and cancer.Scientific reports · 2026Article
- CCL20-CCR6 axis in autoimmune disease and cancer progression: clinical and therapeutic implications.Cell communication and signaling : CCS · 2026Review
- Targeting IBD treatment: smart drug delivery systems for oral administration.Materials today. Bio · 2026Review
- Integrating multi-omics and machine learning to uncover CCL20 as a potential regulator of the immunosuppressive microenvironment in lung adenocarcinoma.Frontiers in immunology · 2026Article
- Cytokine and chemokine networks in colorectal cancer.Frontiers in immunology · 2026Review
- Bioinformatics-based screening and prediction of compounds and antigen epitopes for immune targets with point mutations in colitis-associated colorectal cancer.Discover oncology · 2025Article
- Interplay between acute Type A aortic dissection and pan-cancer: Clinical evidence, bioinformatics, and experimental validation.iScience · 2025Article
- Intestinal epithelialActa biochimica et biophysica Sinica · 2025Article
- Gene expression regulation and polyadenylation in ulcerative colitis via long-chain RNA sequencing.BMC genomics · 2025Article
- Characterizing macrophage diversity in colorectal malignancies through single-cell genomics.Frontiers in immunology · 2025Review
- Qi Yin San Liang San Decoction Relieves Gefitinib-Induced Diarrhea via the Modulation of Chemokines and Innate Immune Responses.Current topics in medicinal chemistry · 2025Article
- Impact of hypercoagulable state on Crohn's disease severity and progression: transcriptomic and single-cell analyses of the ileum.Frontiers in immunology · 2025Article
- Identifying Chemokine System-Related Phenotype to Predict Immune Feature in Pan-Cancer and Prognostic Signature for Lung Adenocarcinoma.Journal of inflammation research · 2025Article
- Inflammation and cancer: molecular mechanisms and clinical consequences.Frontiers in oncology · 2025Review
- Interactions between NAD+ metabolism and immune cell infiltration in ulcerative colitis: subtype identification and development of novel diagnostic models.Frontiers in immunology · 2025Article
- Exploring the molecular mechanisms and therapeutic potential of SMAD4 in colorectal cancer.Cancer biology & therapy · 2024Review
- Progress of CCL20-CCR6 in the airways: a promising new therapeutic target.Journal of inflammation (London, England) · 2024Review
- Pentraxin-3 modulates hepatocyte ferroptosis and the innate immune response in LPS-induced liver injury.Molecular biomedicine · 2024Article
- Silencing SMAD4 inhibits inflammation and ferroptosis in asthma by blocking the IL-17A signaling pathway.Respiratory research · 2024Article
- Epithelial-specific loss of Smad4 alleviates the fibrotic response in an acute colitis mouse model.Life science alliance · 2024Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 1 country.
Funding
Abstract
BACKGROUND &
aimsWe previously reported that colon epithelial cell silencing of Smad4 increased epithelial expression of inflammatory genes, including the chemokine c-c motif chemokine ligand 20 (CCL20), and increased susceptibility to colitis-associated cancer. Here, we examine the role of the chemokine/receptor pair CCL20/c-c motif chemokine receptor 6 (CCR6) in mediating colitis-associated colon carcinogenesis induced by SMAD4 loss.
methodsIn silico analysis of SMAD4, CCL20, and CCR6 messenger RNA expression was performed on published transcriptomic data from human ulcerative colitis (UC), and colon and rectal cancer samples. Immunohistochemistry for CCL20 and CCR6 was performed on human tissue microarrays comprising human UC-associated cancer specimens, Mice with conditional, epithelial-specific Smad4 loss with and without germline deletion of the Ccr6 gene were subjected to colitis and followed for up to 3 months. Tumors were quantified histologically, and immune cell populations were analyzed by flow cytometry and immunostaining.
resultsIn human UC-associated cancers, loss of epithelial SMAD4 was associated with increased CCL20 expression and CCR6+ cells. SMAD4 loss in mouse colon epithelium led to enlarged gut-associated lymphoid tissues and recruitment of immune cells to the mouse colon epithelium and stroma, particularly T regulatory, T
conclusionsRegulation of mucosal inflammation is central to SMAD4 tumor suppressor function in the colon. A key downstream node in this regulation is suppression of epithelial CCL20 signaling to CCR6 in immune cells. Loss of SMAD4 in the colon epithelium increases CCL20 expression and chemoattraction of CCR6+ immune cells, contributing to greater susceptibility to colon cancer.
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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 Socratic graph.