ArticleCancer research2014
Novel mechanistic insights into ectodomain shedding of EGFR Ligands Amphiregulin and TGF-α: impact on gastrointestinal cancers driven by secondary bile acids.
Article in Cancer research, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 80 papers, 2 of them syntheses that pooled it.
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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
80 citing papers in PubMed, 2 syntheses or guidelines pooled it, 109 citations in OpenAlex.
- Cholecystectomy promotes the development of colorectal cancer by the alternation of bile acid metabolism and the gut microbiota.Frontiers in medicine · 2022Pooled it
- Cholecystectomy can increase the risk of colorectal cancer: A meta-analysis of 10 cohort studies.PloS one · 2017Pooled it
- Exercise Modulates Microbial Metabolites and Induces Stromal Remodeling in Pancreatic Cancer.Cancer research · 2026Article
- Gut microbiota modulation of gastrointestinal cancers: from dysbiosis signatures to therapeutic interventions.Acta pharmacologica Sinica · 2026Review
- The Role of Selected Bacteria in Breast Cancer Initiation and Development.International journal of molecular sciences · 2026Review
- Effects and mechanism ofWorld journal of gastroenterology · 2026Article
- Sensitising PDAC to Gemcitabine by Suppressing NF-κB Pathway and Enhancing Apoptosis.Pharmaceuticals (Basel, Switzerland) · 2026Article
- Prognostic and Diagnostic Value of Serum Bile Acid Profiles in Pancreatic Cancer: a Retrospective Multicenter Cohort Study.Journal of gastrointestinal cancer · 2026Article
- Host-microbial co-metabolites: from biogenesis to immunomodulation and implications for health and disease.Frontiers in immunology · 2026Review
- Review
- Association between prediagnostic serum metabolites and pancreatic ductal adenocarcinoma risk in two prospective cohorts.International journal of cancer · 2025Article
- In-silico investigation reveals microbial metabolic biomarkers and their regulatory roles in hormone sensitive cancers.Journal, genetic engineering & biotechnology · 2025Article
- The Impact of Cholecystectomy on Colorectal Cancer Risk: A Comprehensive Review on Risk Factors and the Association.Current gastroenterology reports · 2025Review
- Amphiregulin in Fibrotic Diseases and Cancer.International journal of molecular sciences · 2025Review
- The Oncogenic Burden of Obesity: Mechanistic Links Between Adiposity and Gastrointestinal Cancers-A Comprehensive Narrative Review.Biomedicines · 2025Review
- Crosstalk Between Bile Acids and Intestinal Epithelium: Multidimensional Roles of Farnesoid X Receptor and Takeda G Protein Receptor 5.International journal of molecular sciences · 2025Review
- Article
- From Microbiome to Malignancy: Unveiling the Gut Microbiome Dynamics in Pancreatic Carcinogenesis.International journal of molecular sciences · 2025Review
- The Impact of Microwave Ablation on Recurrence and Metastasis of Hepatocellular Carcinoma: Insights From Animal Studies and Cytokine Profiling.Journal of hepatocellular carcinoma · 2025Article
- Co-expression of immune checkpoints in glioblastoma revealed by single-nucleus RNA sequencing and spatial transcriptomics.Computational and structural biotechnology journal · 2024Article
20 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
7 authors at 3 institutions in 1 country.
Funding
Abstract
Secondary bile acids (BA) such as deoxycholic acid (DCA) promote the development of several gastrointestinal malignancies, but how they mediate this effect is unclear. In this study, we offer evidence of a mechanism involving ectodomain shedding of the EGFR ligands amphiregulin (AREG) and TGF-α, which rely upon the cell surface protease TACE/ADAM-17. Specifically, we show that AREG participates in DCA-induced EGFR and STAT3 signaling, cell-cycle progression, and tumorigenicity in human colorectal cancer and pancreatic ductal adenocarcinoma (PDAC). TACE and AREG, but not TGF-α, were overexpressed in both colorectal cancer and PDAC tissues compared with normal tissues. Exposure of colorectal cancer and PDAC cells to DCA resulted in colocalization of Src and TACE to the cell membrane, resulting in AREG-dependent activation of EGFR, mitogen-activated protein kinase (MAPK), and STAT3 signaling. Src or TACE inhibition was sufficient to attenuate DCA-induced AREG, but not TGF-α shedding. We also examined a role for the BA transporter TGR5 in DCA-mediated EGFR and STAT3 signaling. RNA interference-mediated silencing of TGR5 or AREG inhibited DCA-induced EGFR, MAPK, and STAT3 signaling, blunted cyclin D1 expression and cell-cycle progression, and attenuated DCA-induced colorectal cancer or PDAC tumorigenicity. Together, our findings define an AREG-dependent signaling pathway that mediates the oncogenic effects of secondary BAs in gastrointestinal cancers, the targeting of which may enhance therapeutic responses in their treatment.
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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.