Scrib is required for epithelial cell identity and prevents epithelial to mesenchymal transition in the mouse
Open accessAbstract
The integrity and function of epithelial tissues depend on the establishment and maintenance of defining characteristics of epithelial cells, cell-cell adhesion and cell polarity. Disruption of these characteristics can lead to the loss of epithelial identity through a process called epithelial to mesenchymal transition (EMT), which can contribute to pathological conditions such as tissue fibrosis and invasive cancer. In invertebrates, the epithelial polarity gene scrib plays a critical role in establishing and maintaining cell adhesion and polarity. In this study we asked if the mouse homolog, Scrib, is required for establishment and/or maintenance of epithelial identity in vivo. To do so, we conditionally deleted Scrib in the head ectoderm tissue that gives rise to both the ocular lens and the corneal epithelium. Deletion of Scrib in the lens resulted in a change in epithelial cell shape from cuboidal to flattened and elongated. Early in the process, the cell adhesion protein, E-cadherin, and apical polarity protein, ZO-1, were downregulated and the myofibroblast protein, αSMA, was upregulated, suggesting EMT was occurring in the Scrib deficient lenses. Correlating temporally with the upregulation of αSMA, Smad3 and Smad4, TGFβ signaling intermediates, accumulated in the nucleus and Snail, a TGFβ target and transcriptional repressor of the gene encoding E-cadherin, was upregulated. Pax6, a lens epithelial transcription factor required to maintain lens epithelial cell identity also was downregulated. Loss of Scrib in the corneal epithelium also led to molecular changes consistent with EMT, suggesting that the effect of Scrib deficiency was not unique to the lens. Together, these data indicate that mammalian Scrib is required to maintain epithelial identity and that loss of Scrib can culminate in EMT, mediated, at least in part, through TGFβ signaling.
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Scribble is required for directional migration, promotes epithelial identity, and suppresses epithelial-to-mesenchymal transition in mammary and corneal epithelial cells.
“In addition, Scribble is required for directional migration, promotes epithelial identity and suppresses epithelial to mesenchymal transition in mammary and corneal epithelial cells (4, 5, 39).”
From Mislocalization of the Cell Polarity Protein Scribble Promotes Mammary Tumorigenesis and Is Associated with Basal Breast Cancer (2014) · cites this paper as [5]
Scribble plays a clear role in the ectoderm-derived lens and corneal epithelium.
“Scribble plays a clear role in the ectoderm-derived lens and corneal epithelium (Yamben et al., 2013).”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Yamben et al., 2013
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- Authors
- Yamben, I. F., Rachel, R. A., Shatadal, S., Copeland, N. G., Jenkins, N. A., Warming, S., & Griep, A. E.
- Affiliations
- University of Wisconsin–Madison (US)
- National Cancer Institute (US)
- Corresponding author
- Griep, Anne E.
- ORCID
- Jenkins, Nancy A.
- Venue
- Developmental Biology
- Publisher
- Elsevier BV
- Published
- 2013-12
- Volume
- 384
- Issue
- 1
- Pages
- 41-52
- ISSN
- 0012-1606 (ISSN-L)
- PMC
- PMC3853123
- OpenAlex
- W2067733585
- Cited by
- 50
- References
- 69
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 1 · 2023: 2 · 2022: 3 · 2021: 6 · 2020: 2 · 2019: 7 · 2018: 3 · 2017: 7 · 2016: 7 · 2015: 6 · 2014: 4
- FWCI
- 2.54
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Biology (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- NIH (GM07215, EY09091, CA98428, CA14520, EY016665)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Keywords
- SCRIB, epithelial-mesenchymal transition, epithelial polarity, cell adhesion, E-cadherin, ZO-1, alpha-smooth muscle actin, TGF-beta signaling, Smad3, SMAD4, snails, Pax6, lens epithelium, corneal epithelium, conditional gene deletion, mice
- MeSH terms
- Animals, Cell Adhesion, Epithelial Cells, Lens, Crystalline, Mice, Transgenic, Cadherins, Transforming Growth Factor beta, Intracellular Signaling Peptides and Proteins, Mice, Epithelial-Mesenchymal Transition
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