The DOI matches its Crossref record; 4 of the 4 references it cites were found in a registry or an index.
Genetic programs of epithelial cell plasticity directed by transforming growth factor-β
Open accessAbstract
Epithelial–mesenchymal transitions (EMTs) are an essential manifestation of epithelial cell plasticity during morphogenesis, wound healing, and tumor progression. Transforming growth factor-β (TGF-β) modulates epithelial plasticity in these physiological contexts by inducing EMT. Here we report a transcriptome screen of genetic programs of TGF-β-induced EMT in human keratinocytes and propose functional roles for extracellular response kinase (ERK) mitogen-activated protein kinase signaling in cell motility and disruption of adherens junctions. We used DNA arrays of 16,580 human cDNAs to identify 728 known genes regulated by TGF-β within 4 hours after treatment. TGF-β-stimulated ERK signaling mediated regulation of 80 target genes not previously associated with this pathway. This subset is enriched for genes with defined roles in cell–matrix interactions, cell motility, and endocytosis. ERK-independent genetic programs underlying the onset of EMT involve key pathways and regulators of epithelial dedifferentiation, undifferentiated transitional and mesenchymal progenitor phenotypes, and mediators of cytoskeletal reorganization. The gene expression profiling approach delineates complex context-dependent signaling pathways and transcriptional events that determine epithelial cell plasticity controlled by TGF-β. Investigation of the identified pathways and genes will advance the understanding of molecular mechanisms that underlie tumor invasiveness and metastasis.
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Cites
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Polakis, P. (2000) · Genes & Development · doi:10.1101/gad.14.15.1837 · Cited by 3,183
pl5INK4B is a potentia| effector of TGF-β-induced cell cycle arrest
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Cited by
Molecular mechanisms of epithelial–mesenchymal transition
Lamouille, S., Xu, J., & Derynck, R. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3758 · Cited by 8,091
Park, S.-M., Gaur, A. B., Lengyel, E., & Peter, M. E. (2008) · Genes & Development · doi:10.1101/gad.1640608 · Cited by 2,272
Molecular and cellular mechanisms of liver fibrosis and its regression
Kisseleva, T., & Brenner, D. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-00372-7 · Cited by 2,024
Signaling mechanisms of the epithelial-mesenchymal transition
Gonzalez, D. M., & Medici, D. (2014) · Science Signaling · doi:10.1126/scisignal.2005189 · Cited by 1,721
Li, R., Liang, J., Ni, S., Zhou, T., Qing, X., Li, H., He, W., Chen, J., Li, F., Zhuang, Q., et al. (2010) · Cell Stem Cell · doi:10.1016/j.stem.2010.04.014 · Cited by 1,072
Metadata
- Authors
- Zavadil, J., Bitzer, M., Liang, D., Yang, Y.-C., Massimi, A., Kneitz, S., Piek, E., & Böttinger, E. P.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2001-06-05
- Volume
- 98
- Issue
- 12
- Pages
- 6686-6691
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2082438422
- Cited by
- 536
- References
- 4
- FWCI
- 10.42
- Type
- journal article
- Language
- en
- Open access
- green
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- Zavadil, J., Bitzer, M., Liang, D., Yang, Y.-C., Massimi, A., Kneitz, S., Piek, E., & Böttinger, E. P. (2001). Genetic programs of epithelial cell plasticity directed by transforming growth factor-β. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.111614398
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