ArticleScientific reports2020
Increased stiffness of the tumor microenvironment in colon cancer stimulates cancer associated fibroblast-mediated prometastatic activin A signaling.
Article in Scientific reports, 2020. 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 92 papers, 1 of them a synthesis 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
92 citing papers in PubMed, 1 synthesis or guideline pooled it, 126 citations in OpenAlex.
- Research hotspots and frontiers in the tumor microenvironment of colorectal cancer: a bibliometric study from 2014 to 2024.Frontiers in oncology · 2025Pooled it
- Localized Hydrogel-Based Therapeutics: A Strategic Approach to Mitigating Postoperative Recurrence in Breast Cancer.Polymers · 2026Review
- Therapeutic Strategies Targeting the Tumor-Stromal Microenvironment in Colorectal Cancer: A Narrative Review.Targeted oncology · 2026Review
- Tailorable porous collagen hydrogels as a physiologically relevant platform for extrachromosomal DNA-associated colorectal cancer research.Theranostics · 2026Article
- Oncofetal reprogramming and cellular plasticity in colorectal cancer: from mechanisms to clinical translation.Frontiers in oncology · 2026Review
- Activin A-Targeted Therapy in Cancer: An Updated Review on Challenges and Opportunities in Clinical Translation.Current pharmaceutical design · 2026Review
- Development of a 3D Human Colon Model Along with Bioelectronics for the Induction and Monitoring of Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Oncotransformation in Bhas 42 Cell Transformation Assay by Typical Non-Genotoxic Carcinogens, PFOA and PFOS, and Time-Course Transcriptome Analysis.Biomolecules · 2025Article
- 3D Bioprinting and Artificial Intelligence for Tumor Microenvironment Modeling: A Scoping Review of Models, Methods, and Integration Pathways.Molecular pharmaceutics · 2025Article
- Minimally Invasive Bowel Cancer Detection through Vibrating Microrobot-Induced Elastography.Advanced intelligent systems (Weinheim an der Bergstrasse, Germany) · 2025Article
- Article
- Tissue mechanics in tumor heterogeneity and aggression.Trends in cancer · 2025Review
- Tumor Organoids Grown in Mixed-Composition Hydrogels Recapitulate the Plasticity of Pancreatic Cancers.Gels (Basel, Switzerland) · 2025Article
- Setup of an In Vitro Three-Dimensional Stromalized Prostate Cancer Model Using Gelatin Microparticles.ACS omega · 2025Article
- Exploring racial differences in second-harmonic-generation-based prognostic indicators of metastasis in breast and colon cancer.Biophotonics discovery · 2025Article
- Click Hydrogels to Assess Stiffness-Induced Activation of Pancreatic Cancer-Associated Fibroblasts and Its Impact on Cancer Cell Spreading.Chembiochem : a European journal of chemical biology · 2025Article
- Review
- The first embryo, the origin of cancer and animal phylogeny. V. Cancer stem cells as the unifying biomechanical principle between embryology and oncology.Mechanobiology in medicine · 2025Review
- Mechanisms and Strategies to Overcome Drug Resistance in Colorectal Cancer.International journal of molecular sciences · 2025Review
- Decoupling chemical and mechanical signaling in colorectal cancer cell migration.Scientific reports · 2025Article
32 more citing papers are in PubMed but not listed here.
Corrections and comments
- Erratum issued
Authors and funding
9 authors at 3 institutions in 3 countries.
Funding
Abstract
Colorectal cancer (CRC) is the second deadliest cancer in the US due to its propensity to metastasize. Stromal cells and especially cancer-associated fibroblasts (CAF) play a critical biophysical role in cancer progression, but the precise pro-metastatic mechanisms are not clear. Activin A, a TGF-β family member, is a strong pro-metastatic cytokine in the context of CRC. Here, we assessed the link between biophysical forces and pro-metastatic signaling by testing the hypothesis that CAF-generated mechanical forces lead to activin A release and associated downstream effects. Consistent with our hypothesis, we first determined that stromal activin A secretion increased with increasing substrate stiffness. Then we found that stromally-secreted activin A induced ligand-dependent CRC epithelial cell migration and epithelial to mesenchymal transition (EMT). In addition, serum activin A levels are significantly increased in metastatic (stage IV) CRC patients (1.558 ng/ml versus 0.4179 ng/ml, p < 0.05). We propose that increased tumor microenvironment stiffness leads to stromal cell-mediated TGF-β family signaling relying on the induction and utilization of activin A signaling.
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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.