ArticleInternational journal of biological sciences2020
Cancer-associated Fibroblasts induce epithelial-mesenchymal transition
Article in International journal of biological sciences, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 68 papers.
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Who cites it
68 citing papers in PubMed, 106 citations in OpenAlex.
- Cancer-associated fibroblasts in therapeutic resistance of hepatocellular carcinoma: evidence, mechanisms, and translational implications.Medical oncology (Northwood, London, England) · 2026Review
- Role of epithelial-mesenchymal transition (EMT) in malignancies: current status and future prospects.Signal transduction and targeted therapy · 2026Review
- Signalling pathways in hepatocellular carcinoma (HCC) metastasis and invasion: Molecular mechanisms and therapeutic implications.Biochemistry and biophysics reports · 2026Review
- Sublethal heat stress synergizes with the tumor microenvironment to drive recurrence of hepatocellular carcinoma after thermal ablation: mechanisms, molecular predictors, and targeted interventions.Cell biology and toxicology · 2026Review
- Cancer-associated fibroblasts, clinicopathological characteristics and prognosis of liver cancer: A systematic review and meta-analysis based on real-world research.World journal of gastrointestinal oncology · 2025Article
- Cancer-Associated Fibroblasts: Origin, Classification, Tumorigenicity, and Targeting for Cancer Therapy.MedComm · 2025Review
- The heterogeneous roles of neutrophils in gastric cancer: scaffold or target?Cellular & molecular biology letters · 2025Review
- Tgm2-Catalyzed Covalent Cross-Linking of IκBα Drives NF-κB Nuclear Translocation to Promote SASP in Senescent Microglia.Aging cell · 2025Article
- Targeted therapy and immunotherapy for gastric cancer: rational strategies, novel advancements, challenges, and future perspectives.Molecular medicine (Cambridge, Mass.) · 2025Review
- Cancer-associated fibroblasts induce almonertinib resistance in non-small cell lung cancer.Journal of translational medicine · 2025Article
- The role of transcription factors in the crosstalk between cancer-associated fibroblasts and tumor cells.Journal of advanced research · 2025Review
- Lactylation in Tumor Immune Escape and Immunotherapy: Multifaceted Functions and Therapeutic Strategies.Research (Washington, D.C.) · 2025Review
- Advances in Tumor Microenvironment and Immunotherapeutic Strategies for Hepatocellular Carcinoma.Oncology research · 2025Review
- Role of FHOD1 in tumor cells and tumor immune microenvironment.Frontiers in immunology · 2025Review
- SpottedPy quantifies relationships between spatial transcriptomic hotspots and uncovers environmental cues of epithelial-mesenchymal plasticity in breast cancer.Genome biology · 2024Article
- Heterogeneity and interplay: the multifaceted role of cancer-associated fibroblasts in the tumor and therapeutic strategies.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2024Review
- The double-edged effects of IL-6 in liver regeneration, aging, inflammation, and diseases.Experimental hematology & oncology · 2024Review
- pH/GSH dual-responsive nanoparticle for auto-amplified tumor therapy of breast cancer.Journal of nanobiotechnology · 2024Article
- Cancer‑associated fibroblasts under therapy‑induced senescence in the tumor microenvironment (Review).Experimental and therapeutic medicine · 2024Review
- The Role of Transglutaminase 2 in Cancer: An Update.International journal of molecular sciences · 2024Review
8 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
21 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) play crucial roles in enhancing cell survival, proliferation, invasion, and metastasis. We previously showed that hepatocellular carcinoma-derived CAFs (H-CAFs) promoted proliferation of hepatocellular carcinoma (HCC) cells. This study aimed to further explore the role of CAFs in HCC epithelial-mesenchymal transition (EMT) and the underlying mechanism. High CAF density was significantly associated with liver cirrhosis, inferior clinicopathologic characteristics, elevated EMT-associated markers, and poorer survival in human HCC. Within HCC cells, EMT was induced after co-culture with H-CAFs. Secretomic analysis showed that IL-6 and HGF were the key EMT-stimulating cytokines secreted by H-CAFs. Proteomic analysis revealed that TG2 was significantly upregulated in HCC cells with EMT phenotypes. Overexpression of TG2 promoted EMT of HCC cells, and knockdown of TG2 remarkably attenuated the H-CAF-induced EMT. Furthermore, during EMT, TG2 expression was enhanced after HCC cells were stimulated by IL-6, but not HGF. Inhibition of the IL-6/STAT3 signaling decreased TG2 expression. The principal TG2 transcription control element and a potential STAT3 binding site were identified using promoter analysis. Hence, H-CAFs facilitates HCC cells EMT mediated by IL-6, which in turn activates IL-6/IL6R/STAT3 axis to promote TG2 expression.
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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.