Hyperproliferation and Defects in Epithelial Polarity upon Conditional Ablation of α-Catenin in Skin
Open accessAbstract
When surface epithelium was conditionally targeted for ablation of alpha-catenin, hair follicle development was blocked and epidermal morphogenesis was dramatically affected, with defects in adherens junction formation, intercellular adhesion, and epithelial polarity. Differentiation occurred, but epidermis displayed hyperproliferation, suprabasal mitoses, and multinucleated cells. In vitro, alpha-catenin null keratinocytes were poorly contact inhibited and grew rapidly. These differences were not dependent upon intercellular adhesion and were in marked contrast to keratinocytes conditionally null for another essential intercellular adhesion protein, desmoplakin (DP). KO keratinocytes exhibited sustained activation of the Ras-MAPK cascade due to aberrations in growth factor responses. Thus, remarkably, features of precancerous lesions often attributed to defects in cell cycle regulatory genes can be generated by compromising the function of alpha-catenin.
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Growth regulation may be a cadherin-independent function of a-catenin.
“Alternatively, growth regulation may be a cadherin-independent function of a-catenin (Vasioukhin et al, 2001).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Vasioukhin et al, 2001
The Discussion (page unavailable in our copy) says α-catenin’s effects on hyperproliferation can be separated from its effects on cell–cell adhesion, supporting a possible growth-regulatory role beyond adhesion. But the paper also links the altered growth signaling to an E-cadherin/β-catenin complex with IRS-1; it does not establish that growth regulation is independent of cadherin itself. (LLM, conf=0.83)
Experimental — accuracy not yet measuredInactivation of a-catenin in the epidermis resulted in severe blistering and overgrowth.
“Inactivation of a-catenin in the epidermis resulted in severe blistering and overgrowth (Vasioukhin et al, 2001).”
From E‐cadherin is essential for in vivo epidermal barrier function by regulating tight junctions (2005) · cites this paper as Vasioukhin et al, 2001
The discussion reports uncontrolled growth and large epidermal masses after α-catenin ablation, supporting the overgrowth claim. Figure 2 reports impaired intercellular junctions in the knockout epidermis, but the passages found do not report severe blistering; that part is unsupported. (LLM, conf=0.85)
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- Authors
- Vasioukhin, V., Bauer, C., Degenstein, L., Wise, B., & Fuchs, E.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Fuchs, Elaine
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2001-02
- Volume
- 104
- Issue
- 4
- Pages
- 605-617
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2112718635
- Cited by
- 435
- References
- 0
- Citations by year
- 2026: 3 · 2025: 3 · 2024: 10 · 2023: 8 · 2022: 10 · 2021: 9 · 2020: 9 · 2019: 8 · 2018: 13 · 2017: 14 · 2016: 12 · 2015: 20 · 2014: 20 · 2013: 23 · 2012: 29
- FWCI
- 8.98
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01AR027883, R01 AR27883)
- National Institute of Dental and Craniofacial Research (5P50DE11921, P50DE011921)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Skin and Cellular Biology Research
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Keywords
- alpha-catenin, conditional gene deletion, epithelial polarity, epidermal morphogenesis, hair follicle development, adherens junctions, cell-cell adhesion, keratinocyte hyperproliferation, desmoplakin, RAS/MAPK pathway, contact inhibition, precancerous lesions, skin
- MeSH terms
- Alleles, Animals, Cell Adhesion, Cell Cycle, Cell Division, Cells, Cultured, Cytoskeletal Proteins, Electrophoresis, Polyacrylamide Gel, Epithelium, Flow Cytometry, Growth Substances, Hair, Intercellular Junctions, Microscopy, Fluorescence, Mitosis, Models, Genetic, Phosphorylation, Precipitin Tests, Skin, Skin Physiological Phenomena, Time Factors, Blotting, Southern, Blotting, Western, Signal Transduction, Keratinocytes, Mice, Knockout, ras Proteins, Hair Follicle, MAP Kinase Signaling System, alpha Catenin, Desmoplakins, Mice
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