ArticleCell death & disease2021
Colorectal cancer-associated fibroblasts promote metastasis by up-regulating LRG1 through stromal IL-6/STAT3 signaling.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 67 papers.
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Who cites it
67 citing papers in PubMed, 125 citations in OpenAlex.
- Cancer Stem Cells in Colorectal Cancer: From Molecular Mechanisms to Diagnosis, Prognosis and Therapy Implications.Cancers · 2026Review
- Review
- PI3K and MAPK Signaling Nodes Serve as Divergent Drivers of Phenotypic Plasticity in Cancer-Associated Fibroblasts in Colorectal Cancer.Cancer research · 2026Article
- Cytokines and cancer-associated fibroblasts.Journal of hematology & oncology · 2026Review
- STK25 inhibits cancer-associated fibroblast activation to overcome cetuximab resistance in colorectal cancer.Clinical and translational medicine · 2026Article
- Hepatocyte-derived LRG1 primes the liver for metastasis and impairs immunotherapy.Cellular & molecular immunology · 2026Article
- Identification and Integration of LRG1-Induced Differentially Expressed Gene (DEG) Hub Profiles in Breast Cancer Cells.International journal of molecular sciences · 2026Article
- Combining AI to reveal CCDC3-mediated pathways of colorectal cancer liver metastasis.NPJ digital medicine · 2026Article
- Key molecular mechanisms and regulatory networks in colorectal cancer liver metastasis.Biological procedures online · 2026Review
- Cancer-associated fibroblasts are associated with CD8+ T cell depletion and poor prognosis in colorectal adenocarcinoma: a multi-omics and machine learning analysis.The journal of pathology. Clinical research · 2026Article
- Revealing the multiple faces of LRG1: gene expression, structure, function, and therapeutic potential.Journal of advanced research · 2026Review
- Modeling CAF-tumor interactions to overcome therapy resistance.Journal of experimental & clinical cancer research : CR · 2026Review
- Emerging nano-immunotherapeutic strategies achieve metastatic colorectal cancer precision therapy.Journal of nanobiotechnology · 2026Review
- Polyp Tissue LRG1 Protein Levels andInternational journal of general medicine · 2026Article
- Aerobic Exercise-Induced TGF-β Receptor Reprogramming Disrupts Neutrophil-Microglia Crosstalk to Attenuate Early Brain Injury after Subarachnoid Hemorrhage.Research (Washington, D.C.) · 2026Article
- Dedifferentiation and metabolic reprogramming of human adipocytes in the tumor niche triggered by colorectal cancer cells.Biological research · 2025Article
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- The role of Fetuin-A and Leucine-rich α-2-glycoprotein in the diagnosis of prostate cancer - a pilot study.Biomedical papers of the Medical Faculty of the University Palacky, Olomouc, Czechoslovakia · 2025Article
- Colorectal Cancer at the Crossroads: The Good, the Bad, and the Future of Platinum-Based Drugs.Chemical reviews · 2025Review
- The critical role of LRG1 in pathological fibrosis.Journal of molecular medicine (Berlin, Germany) · 2025Review
7 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cancer-associated fibroblasts (CAFs) have been shown to play a strong role in colorectal cancer metastasis, yet the underlying mechanism remains to be fully elucidated. Using CRC clinical samples together with ex vivo CAFs-CRC co-culture models, we found that CAFs induce expression of Leucine Rich Alpha-2-Glycoprotein 1(LRG1) in CRC, where it shows markedly higher expression in metastatic CRC tissues compared to primary tumors. We further show that CAFs-induced LRG1 promotes CRC migration and invasion that is concomitant with EMT (epithelial-mesenchymal transition) induction. In addition, this signaling axis has also been confirmed in the liver metastatic mouse model which displayed CAFs-induced LRG1 substantially accelerates metastasis. Mechanistically, we demonstrate that CAFs-secreted IL-6 (interleukin-6) is responsible for LRG1 up-regulation in CRC, which occurs through a direct transactivation by STAT3 following JAK2 activation. In clinical CRC tumor samples, LRG1 expression was positively correlated with CAFs-specific marker, α-SMA, and a higher LRG1 expression predicted poor clinical outcomes especially distant metastasis free survival, supporting the role of LRG1 in CRC progression. Collectively, this study provided a novel insight into CAFs-mediated metastasis in CRC and indicated that therapeutic targeting of CAFs-mediated IL-6-STAT3-LRG1 axis might be a potential strategy to mitigate metastasis in CRC.
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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.