ArticleCarcinogenesis2015
Aberrantly expressed Fra-1 by IL-6/STAT3 transactivation promotes colorectal cancer aggressiveness through epithelial-mesenchymal transition.
Article in Carcinogenesis, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 94 papers.
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Who cites it
94 citing papers in PubMed, 147 citations in OpenAlex.
- Prognostic Impact of IL6 Genetic Variants in Patients with Metastatic Colorectal Cancer Treated with Bevacizumab-Based Chemotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Trial
- Identification and Biological Evaluation of Juglone-Derived STAT3 Inhibitors against Colorectal Cancer.ACS medicinal chemistry letters · 2026Article
- APOE+ macrophages induce tumor cell metastatic characteristics via TNFSF12/TNFRSF12A signaling, correlating with poor patient prognosis.Cancer cell international · 2026Article
- Artificial Intelligence-Enhanced Molecular Profiling of JAK-STAT Pathway Alterations in FOLFOX-Treated Early-Onset Colorectal Cancer.International journal of molecular sciences · 2026Article
- 23-hydroxybetulinic acid induces cell cycle arrest in esophageal cancer cells via the BUB1/STAT3 signaling pathway.Frontiers in oncology · 2026Article
- The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications.Cell biochemistry and biophysics · 2025Review
- Meprin β activity modulates cellular proliferation via trans-signaling IL-6-mediated AKT/ERK pathway in IR-induced kidney injury.BMC nephrology · 2025Article
- Targeting cytokine and chemokine signaling pathways for enhancing chemo-sensitivity in colorectal cancer.Cell communication and signaling : CCS · 2025Review
- The AP-1 factor JUNB correlates with poor survival of patients with esophageal adenocarcinoma.Scientific reports · 2025Article
- Article
- Molecular Regulation of SASP in Cellular Senescence: Therapeutic Implications and Translational Challenges.Cells · 2025Review
- Ethnicity-Specific Molecular Alterations in MAPK and JAK/STAT Pathways in Early-Onset Colorectal Cancer.Cancers · 2025Article
- Deciphering the metabolic landscape of colorectal cancer through the lens of AhR-mediated intestinal inflammation.Discover oncology · 2025Review
- RNA Sequencing Identifies Novel Signaling Pathways and Potential Drug Target Genes Induced by FOSL1 in Glioma Progression and Stemness.Biologics : targets & therapy · 2025Article
- FRA1 (Frontiers in cell and developmental biology · 2025Article
- JAK-STAT Signaling in Autoimmunity and Cancer.ImmunoTargets and therapy · 2025Review
- Regulatory mechanisms of haptoglobin on particulate matter-induced epithelial-to-mesenchymal transition in bronchial epithelial cells.Journal of thoracic disease · 2024Article
- Baitouweng decoction suppresses growth of esophageal carcinoma cells through miR-495-3p/BUB1/STAT3 axis.World journal of gastrointestinal oncology · 2024Article
- Interaction of NF-κB and FOSL1 drives glioma stemness.Cellular and molecular life sciences : CMLS · 2024Article
- FOSL1's Oncogene Roles in Glioma/Glioma Stem Cells and Tumorigenesis: A Comprehensive Review.International journal of molecular sciences · 2024Review
34 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pro-inflammatory cytokine interleukin-6 (IL-6) in tumor microenvironment has been suggested to promote development and progression of colorectal cancer (CRC). However, the underlying molecular mechanisms remain elusive. In this study, we demonstrate that fos-related antigen-1 (Fra-1) plays a critical role in IL-6 induced CRC aggressiveness and epithelial-mesenchymal transition (EMT). In CRC cell lines, the expression of Fra-1 gene was found significantly upregulated during IL-6-driven EMT process. The Fra-1 induction occurred at transcriptional level in a manner dependent on signal transducer and activator of transcription 3 (STAT3), during which both phosphorylated and acetylated post-translational modifications were required for STAT3 activation to directly bind to the Fra-1 promoter. Importantly, RNA interference-based attenuation of either STAT3 or Fra-1 prevented IL-6-induced EMT, cell migration and invasion, whereas ectopic expression of Fra-1 markedly reversed the STAT3-knockdown effect and enhanced CRC cell aggressiveness by regulating the expression of EMT-promoting factors (ZEB1, Snail, Slug, MMP-2 and MMP-9). Furthermore, Fra-1 levels were positively correlated with the local invasion depth as well as lymph node and liver metastasis in a total of 229 CRC patients. Intense immunohistochemical staining of Fra-1 was observed at the tumor marginal area adjacent to inflammatory cells and in parallel with IL-6 secretion and STAT3 activation in CRC tissues. Together, this study proposes the existence of an aberrant IL-6/STAT3/Fra-1 signaling axis leading to CRC aggressiveness through EMT induction, which suggests novel therapeutic opportunities for the malignant disease.
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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.