ArticleEMBO molecular medicine2020
A paracrine activin A-mDia2 axis promotes squamous carcinogenesis via fibroblast reprogramming.
Article in EMBO molecular medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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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
34 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Fibroblasts in Scar Formation: Biology and Clinical Translation.Oxidative medicine and cellular longevity · 2022Pooled it
- Activin A-Targeted Therapy in Cancer: An Updated Review on Challenges and Opportunities in Clinical Translation.Current pharmaceutical design · 2026Review
- Melanoma and its fibroblastic allies: the emerging importance of CAFs in immune suppression, ECM modulation, and therapy resistance.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- MIRO2-mediated mitochondrial transfer from cancer cells induces cancer-associated fibroblast differentiation.Nature cancer · 2025Article
- Bridging the tumor microenvironment: the pivotal role of cancer-associated fibroblasts in tumor cachexia development.Molecular cancer · 2025Review
- Activin A affects colorectal cancer progression and immunomodulation in a stage dependent manner.Scientific reports · 2025Article
- ANKRD1 is a mesenchymal-specific driver of cancer-associated fibroblast activation bridging androgen receptor loss to AP-1 activation.Nature communications · 2024Article
- Context-dependent TGFβ family signalling in cell fate regulation.Nature reviews. Molecular cell biology · 2023Review
- Paracrine activin B-NF-κB signaling shapes an inflammatory tumor microenvironment in gastric cancer via fibroblast reprogramming.Journal of experimental & clinical cancer research : CR · 2023Article
- Activin A-Mediated Polarization of Cancer-Associated Fibroblasts and Macrophages Confers Resistance to Checkpoint Immunotherapy in Skin Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2023Article
- Investigating Mammalian Formins with SMIFH2 Fifteen Years in: Novel Targets and Unexpected Biology.International journal of molecular sciences · 2023Review
- Cancer-Associated Fibroblasts and Extracellular Matrix: Therapeutical Strategies for Modulating the Cholangiocarcinoma Microenvironment.Current oncology (Toronto, Ont.) · 2023Review
- Article
- Sphingosine Kinase 2 in Stromal Fibroblasts Creates a Hospitable Tumor Microenvironment in Breast Cancer.Cancer research · 2023Article
- Signaling pathways in cancer-associated fibroblasts: recent advances and future perspectives.Cancer communications (London, England) · 2023Review
- A Protumorigenic mDia2-MIRO1 Axis Controls Mitochondrial Positioning and Function in Cancer-Associated Fibroblasts.Cancer research · 2022Article
- Review
- Integrated multi-omics reveals cellular and molecular interactions governing the invasive niche of basal cell carcinoma.Nature communications · 2022Article
- Review
- Single-Cell Atlas of Lineage States, Tumor Microenvironment, and Subtype-Specific Expression Programs in Gastric Cancer.Cancer discovery · 2022Article
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Authors and funding
10 authors.
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Abstract
Cancer-associated fibroblasts (CAFs) are key regulators of tumorigenesis and promising targets for next-generation therapies. We discovered that cancer cell-derived activin A reprograms fibroblasts into pro-tumorigenic CAFs. Mechanistically, this occurs via Smad2-mediated transcriptional regulation of the formin mDia2, which directly promotes filopodia formation and cell migration. mDia2 also induces expression of CAF marker genes through prevention of p53 nuclear accumulation, resulting in the production of a pro-tumorigenic matrisome and secretome. The translational relevance of this finding is reflected by activin A overexpression in tumor cells and of mDia2 in the stroma of skin cancer and other malignancies and the correlation of high activin A/mDia2 levels with poor patient survival. Blockade of this signaling axis using inhibitors of activin, activin receptors, or mDia2 suppressed cancer cell malignancy and squamous carcinogenesis in 3D organotypic cultures, ex vivo, and in vivo, providing a rationale for pharmacological inhibition of activin A-mDia2 signaling in stratified cancer patients.
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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.