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Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation
Open accessAbstract
Master regulators of the epithelial-mesenchymal transition such as Twist1 and Snail1 have been implicated in invasiveness and the generation of cancer stem cells, but their persistent activity inhibits stem-cell-like properties and the outgrowth of disseminated cancer cells into macroscopic metastases. Here, we show that Twist1 activation primes a subset of mammary epithelial cells for stem-cell-like properties, which only emerge and stably persist following Twist1 deactivation. Consequently, when cells undergo a mesenchymal-epithelial transition (MET), they do not return to their original epithelial cell state, evidenced by acquisition of invasive growth behavior and a distinct gene expression profile. These data provide an explanation for how transient Twist1 activation may promote all steps of the metastatic cascade; i.e., invasion, dissemination, and metastatic outgrowth at distant sites.
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Cites
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
ROS1 Rearrangements Define a Unique Molecular Class of Lung Cancers
Bergethon, K., Shaw, A. T., Ignatius Ou, S.-H., Katayama, R., Lovly, C. M., McDonald, N. T., Massion, P. P., Siwak-Tapp, C., Gonzalez, A., Fang, R., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.35.6345 · Cited by 1,555
Human breast cancer cells generated by oncogenic transformation of primary mammary epithelial cells
Elenbaas, B., Spirio, L., Koerner, F., Fleming, M. D., Zimonjic, D. B., Donaher, J. L., Popescu, N. C., Hahn, W. C., & Weinberg, R. A. (2001) · Genes & Development · doi:10.1101/gad.828901 · Cited by 878
Epithelial-mesenchymal transitions: insights from development
Lim, J., & Thiery, J. P. (2012) · Development · doi:10.1242/dev.071209 · Cited by 661
Cited by
Nieto, M. A., Huang, R. Y.-J., Jackson, R. A., & Thiery, J. P. (2016) · Cell · doi:10.1016/j.cell.2016.06.028 · Cited by 4,492
New insights into the mechanisms of epithelial–mesenchymal transition and implications for cancer
Dongre, A., & Weinberg, R. A. (2019) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-018-0080-4 · Cited by 3,876
Batlle, E., & Clevers, H. (2017) · Nature Medicine · doi:10.1038/nm.4409 · Cited by 2,769
EMT, CSCs, and drug resistance: the mechanistic link and clinical implications
Shibue, T., & Weinberg, R. A. (2017) · Nature Reviews Clinical Oncology · doi:10.1038/nrclinonc.2017.44 · Cited by 2,539
Epithelial Mesenchymal Transition in Tumor Metastasis
Mittal, V. (2018) · Annual Review of Pathology: Mechanisms of Disease · doi:10.1146/annurev-pathol-020117-043854 · Cited by 1,528
Metadata
- Authors
- Schmidt, J. M., Panzilius, E., Bartsch, H. S., Irmler, M., Beckers, J., Kari, V., Linnemann, J. R., Dragoi, D., Hirschi, B., Kloos, U. J., Sass, S., Theis, F., Kahlert, S., Johnsen, S. A., Sotlar, K., & Scheel, C. H.
- Venue
- Cell Reports
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 10
- Issue
- 2
- Pages
- 131-139
- ISSN
- 2211-1247 (ISSN-L)
- OpenAlex
- W1992380352
- Cited by
- 170
- References
- 4
- FWCI
- 9.23
- Type
- journal article
- Language
- en
- Open access
- gold
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- The paper
- Schmidt, J. M., Panzilius, E., Bartsch, H. S., Irmler, M., Beckers, J., Kari, V., Linnemann, J. R., Dragoi, D., Hirschi, B., Kloos, U. J., Sass, S., Theis, F., Kahlert, S., Johnsen, S. A., Sotlar, K., & Scheel, C. H. (2015). Stem-Cell-like Properties and Epithelial Plasticity Arise as Stable Traits after Transient Twist1 Activation. Cell Reports. https://doi.org/10.1016/j.celrep.2014.12.032
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
