ArticleGastroenterology2011
Toll-like receptor 4 variant D299G induces features of neoplastic progression in Caco-2 intestinal cells and is associated with advanced human colon cancer.
Article in Gastroenterology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 49 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.
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Who cites it
49 citing papers in PubMed, 83 citations in OpenAlex.
- Association of genetic variation in TLR4 and TLR9 genes with susceptibility to invasive ductal breast carcinoma.Molecular biology reports · 2026Article
- The Role of Natural Products from Herbal Medicine in TLR4 Signaling for Colorectal Cancer Treatment.Molecules (Basel, Switzerland) · 2024Review
- Terpenoid-Mediated Targeting of STAT3 Signaling in Cancer: An Overview of Preclinical Studies.Biomolecules · 2024Review
- Pellino 3 promotes the colitis-associated colorectal cancer through suppression of IRF4-mediated negative regulation of TLR4 signalling.Molecular oncology · 2023Article
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- Whole-genome identification and construction of the lncRNA-mRNA co-expression network in patients with actinic keratosis.Translational cancer research · 2022Article
- The Toll-like Receptor 4 Polymorphism Asp299Gly Is Associated with an Increased Risk of Ovarian Cancer.Cells · 2022Article
- Review
- Review
- Association of D299G Polymorphism of TLR4 Gene and CagA Virulence Factor of H. pylori among the Iranian Patients with Colorectal Cancer.Medical journal of the Islamic Republic of Iran · 2022Article
- The expression and prognostic value of toll-like receptors (TLRs) in pancreatic cancer patients treated with neoadjuvant therapy.PloS one · 2022Article
- EMT-cancer cells-derived exosomal miR-27b-3p promotes circulating tumour cells-mediated metastasis by modulating vascular permeability in colorectal cancer.Clinical and translational medicine · 2021Article
- Overview of the STAT-3 signaling pathway in cancer and the development of specific inhibitors.Oncology letters · 2020Review
- LL1, a novel and highly selective STAT3 inhibitor, displays anti-colorectal cancer activities in vitro and in vivo.British journal of pharmacology · 2020Article
- Towards embedding Caco-2 model of gut interface in a microfluidic device to enable multi-organ models for systems biology.BMC systems biology · 2019Article
- Novel imidazopyridine suppresses STAT3 activation by targeting SHP-1.Journal of enzyme inhibition and medicinal chemistry · 2018Article
- Polymorphisms in genes related to inflammation and obesity and colorectal adenoma risk.Molecular carcinogenesis · 2018Article
- STAT3 in Breast Cancer Onset and Progression: A Matter of Time and Context.International journal of molecular sciences · 2018Article
- Prediction of novel target genes and pathways involved in bevacizumab-resistant colorectal cancer.PloS one · 2018Article
- "Do We Know Jack" About JAK? A Closer Look at JAK/STAT Signaling Pathway.Frontiers in oncology · 2018Review
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
Abstract
BACKGROUND &
aimsThe Toll-like receptor (TLR) 4 mediates homeostasis of the intestinal epithelial cell (IEC) barrier. We investigated the effects of TLR4-D299G on IEC functions.
methodsWe engineered IECs (Caco-2) to stably overexpress hemagglutinin-tagged wild-type TLR4, TLR4-D299G, or TLR4-T399I. We performed gene expression profiling using DNA microarray analysis. Findings were confirmed by real-time, quantitative, reverse-transcriptase polymerase chain reaction, immunoblot, enzyme-linked immunosorbent assay, confocal immunofluorescence, and functional analyses. Tumorigenicity was tested using the CD1 nu/nu mice xenograft model. Human colon cancer specimens (N = 214) were genotyped and assessed for disease stage.
resultsCaco-2 cells that expressed TLR4-D299G underwent the epithelial-mesenchymal transition and morphologic changes associated with tumor progression, whereas cells that expressed wild-type TLR4 or TLR4-T399I did not. Caco-2 cells that expressed TLR4-D299G had significant increases in expression levels of genes and proteins associated with inflammation and/or tumorigenesis compared with cells that expressed other forms of TLR4. The invasive activity of TLR4-D299G Caco-2 cells required Wnt-dependent activation of STAT3. In mice, intestinal xenograft tumors grew from Caco-2 cells that expressed TLR4-D299G, but not cells that expressed other forms of TLR4; tumor growth was blocked by a specific inhibitor of STAT3. Human colon adenocarcinomas from patients with TLR4-D299G were more frequently of an advanced stage (International Union Against Cancer [UICC] ≥III, 70% vs 46%; P = .0142) with metastasis (UICC IV, 42% vs 19%; P = .0065) than those with wild-type TLR4. Expression of STAT3 messenger RNA was higher among colonic adenocarcinomas with TLR4-D299G than those with wild-type TLR4.
conclusionsTLR4-D299G induces features of neoplastic progression in intestinal epithelial Caco-2 cells and associates with aggressive colon cancer in humans, implying a novel link between aberrant innate immunity and colonic cancerogenesis.
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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.