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Erk5 Controls Slug Expression and Keratinocyte Activation during Wound Healing
Open accessAbstract
Reepithelialization during cutaneous wound healing involves numerous signals that result in basal keratinocyte activation, spreading, and migration, all linked to a loosening of cell–cell adhesion structures. The transcription factor Slug is required for this process, and EGF treatment of human keratinocytes induced activating phosphorylation of Erk5 that coincides with slug transcription. Accordingly, ectopic activation of Erk5 led to increased Slug mRNA levels and faster wound healing, whereas keratinocyte migration was totally blocked by Erk5 pathway inhibition. Expression of a shRNA specific for Erk5 strongly diminished Erk5 levels in keratinocytes and significantly decreased their motility response to EGF, along with induction of Slug expression. These Erk5-deprived keratinocytes showed an altered, more compact morphology, along with disruption of desmosome organization. Accordingly, they displayed an altered ability to form cell aggregates. These results implicate a novel EGFR/Erk5/Slug pathway in the control of cytoskeleton organization and cell motility in keratinocytes treated with EGF.
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Cites
The snail superfamily of zinc-finger transcription factors
Nieto, M. A. (2002) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm757 · Cited by 1,719
Cited by
Epithelial-Mesenchymal Transitions in Development and Disease
Thiery, J. P., Acloque, H., Huang, R. Y. J., & Nieto, M. A. (2009) · Cell · doi:10.1016/j.cell.2009.11.007 · Cited by 9,931
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
The epigenetics of epithelial-mesenchymal plasticity in cancer
Tam, W. L., & Weinberg, R. A. (2013) · Nature Medicine · doi:10.1038/nm.3336 · Cited by 1,163
Non-redundant functions of EMT transcription factors
Stemmler, M. P., Eccles, R. L., Brabletz, S., & Brabletz, T. (2019) · Nature Cell Biology · doi:10.1038/s41556-018-0196-y · Cited by 524
Cannito, S., Novo, E., di Bonzo, L. V., Busletta, C., Colombatto, S., & Parola, M. (2010) · Antioxidants & Redox Signaling · doi:10.1089/ars.2009.2737 · Cited by 239
Metadata
- Authors
- Arnoux, V., Nassour, M., L'Helgoualc'h, A., Hipskind, R. A., & Savagner, P.
- Venue
- Molecular Biology of the Cell
- Published
- 2008-11
- Volume
- 19
- Issue
- 11
- Pages
- 4738-4749
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- OpenAlex
- W2102024523
- Cited by
- 172
- References
- 1
- FWCI
- 8.21
- Type
- journal article
- Language
- en
- Open access
- green
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- Arnoux, V., Nassour, M., L'Helgoualc'h, A., Hipskind, R. A., & Savagner, P. (2008). Erk5 Controls Slug Expression and Keratinocyte Activation during Wound Healing. Molecular Biology of the Cell. https://doi.org/10.1091/mbc.e07-10-1078
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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