ArticleProceedings of the National Academy of Sciences of the United States of America2019
Stromal-derived interleukin 6 drives epithelial-to-mesenchymal transition and therapy resistance in esophageal adenocarcinoma.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 115 papers.
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Who cites it
115 citing papers in PubMed, 196 citations in OpenAlex.
- Phase II study of pembrolizumab in refractory esophageal cancer with correlates of response and survival.Journal for immunotherapy of cancer · 2021Trial
- Microphysiological models of human gastrointestinal diseases.Nature biomedical engineering · 2026Review
- Targeting the CAF-GDF15 axis attenuates AKT-mediated mitochondrial rewiring and chemoradiation resistance in esophageal adenocarcinoma.Journal of experimental & clinical cancer research : CR · 2026Article
- Cancer-associated fibroblast targeting therapies as a tool to enhance responses to radiotherapy and immunotherapy.Journal for immunotherapy of cancer · 2026Review
- The research advances of crosstalk between cancer-associated fibroblasts and tumor cells using co-culture organoids.Cell death & disease · 2026Review
- Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in multiple cancer types.Experimental hematology & oncology · 2026Review
- Immune-Centered Cross-Talk Between Cancer Cells and the Tumor Microenvironment-Implications for Therapy.Cancers · 2026Review
- Cancer-associated fibroblast-derived interleukin-6 as a key driver of epithelial-mesenchymal transition and metastasis in oral squamous cell carcinoma.Journal of dental sciences · 2026Article
- The neoantigen and associated tumour microenvironment in long-term survivors with oesophageal adenocarcinoma.Frontiers in immunology · 2026Article
- The biology and therapeutic implications of heterogeneity in Barrett oesophagus and oesophageal adenocarcinoma.Nature reviews. Clinical oncology · 2026Review
- Serum levels of the C-terminal pro-peptide of type V collagen have prognostic potential and are associated with a normal subtype of desmoplasia in a retrospective cohort of patients with esophagogastric cancer.Therapeutic advances in medical oncology · 2026Article
- The kinase ERK plays a conserved dominant role in the heterogeneity of epithelial-mesenchymal transition in pancreatic cancer cells.Science signaling · 2025Article
- Crosstalk between cancer‑associated fibroblasts and inflammation in tumor microenvironment: A novel perspective in cancer therapy (Review).Oncology reports · 2025Review
- Deciphering Breast Tumor Heterogeneity Through Patient-Derived Organoids and Circulating Tumor Cells.Journal of personalized medicine · 2025Review
- Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of esophageal adenocarcinoma.Nature cancer · 2025Article
- Cancer‑associated fibroblasts: a pivotal regulator of tumor microenvironment in the context of radiotherapy.Cell communication and signaling : CCS · 2025Review
- Opioid System and Epithelial-Mesenchymal Transition.Pharmaceuticals (Basel, Switzerland) · 2025Review
- Aging-associated mechanisms and metabolic vulnerabilities in esophageal carcinoma: an integrative review.Frontiers in cell and developmental biology · 2025Review
- Integration of Multi-Scale Profiling and Machine Learning Reveals the Prognostic Role of Extracellular Matrix-Related Cancer-Associated Fibroblasts in Lung Adenocarcinoma.International journal of medical sciences · 2025Article
- Metabolic reprogramming and immunological changes in the microenvironment of esophageal cancer: future directions and prospects.Frontiers in immunology · 2025Review
55 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
19 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Esophageal adenocarcinoma (EAC) has a dismal prognosis, and survival benefits of recent multimodality treatments remain small. Cancer-associated fibroblasts (CAFs) are known to contribute to poor outcome by conferring therapy resistance to various cancer types, but this has not been explored in EAC. Importantly, a targeted strategy to circumvent CAF-induced resistance has yet to be identified. By using EAC patient-derived CAFs, organoid cultures, and xenograft models we identified IL-6 as the stromal driver of therapy resistance in EAC. IL-6 activated epithelial-to-mesenchymal transition in cancer cells, which was accompanied by enhanced treatment resistance, migratory capacity, and clonogenicity. Inhibition of IL-6 restored drug sensitivity in patient-derived organoid cultures and cell lines. Analysis of patient gene expression profiles identified ADAM12 as a noninflammation-related serum-borne marker for IL-6-producing CAFs, and serum levels of this marker predicted unfavorable responses to neoadjuvant chemoradiation in EAC patients. These results demonstrate a stromal contribution to therapy resistance in EAC. This signaling can be targeted to resensitize EAC to therapy, and its activity can be measured using serum-borne markers.
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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 OpenQuestion graph.