The mammalian Scribble polarity protein regulates epithelial cell adhesion and migration through E-cadherin
Open accessAbstract
Scribble (Scrib) is a conserved polarity protein required in Drosophila melanogaster for synaptic function, neuroblast differentiation, and epithelial polarization. It is also a tumor suppressor. In rodents, Scrib has been implicated in receptor recycling and planar polarity but not in apical/basal polarity. We now show that knockdown of Scrib disrupts adhesion between Madin–Darby canine kidney epithelial cells. As a consequence, the cells acquire a mesenchymal appearance, migrate more rapidly, and lose directionality. Although tight junction assembly is delayed, confluent monolayers remain polarized. These effects are independent of Rac activation or Scrib binding to βPIX. Rather, Scrib depletion disrupts E-cadherin–mediated cell–cell adhesion. The changes in morphology and migration are phenocopied by E-cadherin knockdown. Adhesion is partially rescued by expression of an E-cadherin–α-catenin fusion protein but not by E-cadherin–green fluorescent protein. These results suggest that Scrib stabilizes the coupling between E-cadherin and the catenins and are consistent with the idea that mammalian Scrib could behave as a tumor suppressor by regulating epithelial cell adhesion and migration.
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In MDCK cells, moderate reduction of Scribble reduces Ecad-dependent cell adhesion and delays both the mesenchymal-to-epithelial transition and tight junction assembly, but cells eventually polarize and become epithelial.
“In MDCK cells, the consequences of Scribble knockdown depend on the level of protein reduction. Moderate reduction reduces Ecad-dependent cell adhesion and delays both the mesenchymal-to-epithelial transition and tight junction assembly. However, cells eventually polarize and become epithelial (Qin et al., 2005).”
From Scribble: A master scaffold in polarity, adhesion, synaptogenesis, and proliferation (2019) · cites this paper as Qin et al., 2005
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- Authors
- Qin, Y., Capaldo, C., Gumbiner, B. M., & Macara, I. G.
- Affiliations
- University of Virginia (US)
- Venue
- The Journal of Cell Biology
- Publisher
- Rockefeller University Press
- Published
- 2005-12-12
- Volume
- 171
- Issue
- 6
- Pages
- 1061-1071
- ISSN
- 0021-9525 (ISSN-L)
- 1540-8140
- PMC
- PMC2171311
- OpenAlex
- W2052131905
- Cited by
- 285
- References
- 52
- Citations by year
- 2026: 10 · 2025: 5 · 2024: 9 · 2023: 12 · 2022: 11 · 2021: 10 · 2020: 8 · 2019: 15 · 2018: 12 · 2017: 18 · 2016: 17 · 2015: 13 · 2014: 16 · 2013: 15 · 2012: 26
- FWCI
- 7.98
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- The Journal of Cell Biology (publishedVersion)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Cancer Institute (P01CA040042, CA 040042)
- National Institute of General Medical Sciences (GM 070902, R01GM070902)
- Topics
- Health Sciences › Medicine › Immunology and Allergy › Cell Adhesion Molecules Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular Mechanics and Interactions
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Hippo pathway signaling and YAP/TAZ
- Keywords
- Scribble, epithelial polarity, E-cadherin, cell-cell adhesion, cell migration, tight junction assembly, catenins, alpha-catenin, mesenchymal transition, tumor suppressor, MDCK cells, planar cell polarity, betaPIX
- MeSH terms
- Animals, Cell Adhesion, Cell Count, Cell Movement, Cells, Cultured, Dogs, Epithelial Cells, Fluorescent Antibody Technique, Humans, Membrane Proteins, Phenotype, Protein Binding, Transfection, Cadherins, Microscopy, Confocal, Cell Cycle Proteins, Guanine Nucleotide Exchange Factors, Gene Silencing, Tumor Suppressor Proteins, RNA Interference, alpha Catenin, Rho Guanine Nucleotide Exchange Factors
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