ArticleMolecular cancer2015
Activin and TGFβ use diverging mitogenic signaling in advanced colon cancer.
Article in Molecular cancer, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 63 citations in OpenAlex.
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- Decoupling chemical and mechanical signaling in colorectal cancer cell migration.Scientific reports · 2025Article
- PDCD10 promotes the tumor-supporting functions of TGF-β in pancreatic cancer.Clinical science (London, England : 1979) · 2024Article
- Epicardial EMT and cardiac repair: an update.Stem cell research & therapy · 2024Review
- Activin A signaling stimulates neutrophil activation and macrophage migration in pancreatitis.Scientific reports · 2024Article
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- Mechanotransduction pathways in regulating epithelial-mesenchymal plasticity.Current opinion in cell biology · 2023Review
- Signaling-induced systematic repression of miRNAs uncovers cancer vulnerabilities and targeted therapy sensitivity.Cell reports. Medicine · 2023Article
- Multi-omic analysis reveals metabolic pathways that characterize right-sided colon cancer liver metastasis.Cancer letters · 2023Article
- KMT2D links TGF-β signaling to noncanonical activin pathway and regulates pancreatic cancer cell plasticity.International journal of cancer · 2023Article
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- A therapeutic target for CKD: activin A facilitates TGFβ1 profibrotic signaling.Cellular & molecular biology letters · 2023Article
- Inhibition of anti-tumor immunity by melanoma cell-derived Activin-A depends on STING.Frontiers in immunology · 2023Article
- The difficulty in translating the preclinical success of combined TGFβ and immune checkpoint inhibition to clinical trial.EBioMedicine · 2022Review
- Prognostic impact of activin subunit inhibin beta A in gastric and esophageal adenocarcinomas.BMC cancer · 2022Article
- Competition between type I activin and BMP receptors for binding to ACVR2A regulates signaling to distinct Smad pathways.BMC biology · 2022Article
- TGFβ Signaling in the Pancreatic Tumor Microenvironment.Cancers · 2021Review
- Activin a Receptor Type 2A Mutation Affects the Tumor Biology of Microsatellite Instability-High Gastric Cancer.Journal of gastrointestinal surgery : official journal of the Society for Surgery of the Alimentary Tract · 2021Article
- Dual Roles of the Activin Signaling Pathway in Pancreatic Cancer.Biomedicines · 2021Review
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
backgroundUnderstanding cell signaling pathways that contribute to metastatic colon cancer is critical to risk stratification in the era of personalized therapeutics. Here, we dissect the unique involvement of mitogenic pathways in a TGFβ or activin-induced metastatic phenotype of colon cancer.
methodMitogenic signaling/growth factor receptor status and p21 localization were correlated in primary colon cancers and intestinal tumors from either AOM/DSS treated ACVR2A (activin receptor 2) -/- or wild type mice. Colon cancer cell lines (+/- SMAD4) were interrogated for ligand-induced PI3K and MEK/ERK pathway activation and downstream protein/phospho-isoform expression/association after knockdown and pharmacologic inhibition of pathway members. EMT was assessed using epithelial/mesenchymal markers and migration assays.
resultsIn primary colon cancers, loss of nuclear p21 correlated with upstream activation of activin/PI3K while nuclear p21 expression was associated with TGFβ/MEK/ERK pathway activation. Activin, but not TGFβ, led to PI3K activation via interaction of ACVR1B and p85 independent of SMAD4, resulting in p21 downregulation. In contrast, TGFβ increased p21 via MEK/ERK pathway through a SMAD4-dependent mechanism. While activin induced EMT via PI3K, TGFβ induced EMT via MEK/ERK activation. In vivo, loss of ACVR2A resulted in loss of pAkt, consistent with activin-dependent PI3K signaling.
conclusionAlthough activin and TGFβ share growth suppressive SMAD signaling in colon cancer, they diverge in their SMAD4-independent pro-migratory signaling utilizing distinct mitogenic signaling pathways that affect EMT. p21 localization in colon cancer may determine a dominant activin versus TGFβ ligand signaling phenotype warranting further validation as a therapeutic biomarker prior to targeting TGFβ family receptors.
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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.