Contextual Determinants of TGF-β Action in Development, Immunity and Cancer
By Charles J. David, J. Massagué. Nature reviews. Molecular cell biology, 2018
701 citations recorded by the source corpus.
Few cell signals match the impact of the transforming growth factor-β (TGFβ) family in metazoan biology. TGFβ cytokines regulate cell fate decisions during development, tissue homeostasis and regeneration, and are major players in tumorigenesis, fibrotic disorders, immune malfunctions and various congenital diseases. The effects of the TGFβ family are mediated by a combinatorial set of ligands and receptors and by a common set of receptor-activated mothers against decapentaplegic homologue (SMAD) transcription factors, yet the effects can differ dramatically depending on the cell type and the conditions. Recent progress has illuminated a model of TGFβ action in which SMADs bind genome-wide in partnership with lineage-determining transcription factors and additionally integrate inputs from other pathways and the chromatin to trigger specific cellular responses. These new insights clarify the operating logic of the TGFβ pathway in physiology and disease. Transforming growth factor-β (TGFβ) family cytokines are important regulators of cell fate with pleiotropic roles in development, tissue homeostasis, regeneration and tumorigenesis. Recent studies revealed that this context dependency relies on the convergence between TGFβ signals and other contextual inputs, whereby transcription factors downstream of these pathways collaboratively act to regulate gene expression.
Subfields: Molecular Biology, Pathology and Forensic Medicine
View Paper: https://www.semanticscholar.org/paper/6a22a0fb0af61071f99c7ddb177a25a9c0bd8690
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In Molecular Biology
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In Pathology and Forensic Medicine
Citations in the corpus
- TGF-β-Mediated Epithelial-Mesenchymal Transition and Cancer Metastasis (2019, positive): “Under physiological conditions, the immune system is the most important element of human defense against cancer, and T lymphocytes and natural killer cells can recognize and specifically clear tumor cells [4,234].”
- Integrin Signaling in Cancer: Mechanotransduction, Stemness, Epithelial Plasticity, and Therapeutic Resistance (2019, background): “In fact, it is well established that mutations of the TGF-β target genes CDKN2B and CDKN1A debilitate TGF-β’s cytostatic program and empower TGF-β signaling to implement its pro-invasive program, often through an EMT (David and Massague, 2018).”
- Oxidative Stress in Cancer (2020, background): “Induction of EMT-TFs by TGF-β signaling is heightened considerably by input from the RAS-MAPK pathway (David and Massague, 2018).”