mTOR mediates Wnt-induced epidermal stem cell exhaustion and aging
Open accessAbstract
Epidermal integrity is a complex process established during embryogenesis and maintained throughout the organism lifespan by epithelial stem cells. Although Wnt regulates normal epithelial stem cell renewal, aberrant Wnt signaling can contribute to cancerous growth. Here, we explored the consequences of persistent expressing Wnt1 in an epidermal compartment that includes the epithelial stem cells. Surprisingly, Wnt caused the rapid growth of the hair follicles, but this was followed by epithelial cell senescence, disappearance of the epidermal stem cell compartment, and progressive hair loss. Although Wnt1 induced the activation of beta-catenin and the mTOR pathway, both hair follicle hyperproliferation and stem cell exhaustion were strictly dependent on mTOR function. These findings suggest that whereas activation of beta-catenin contributes to tumor growth, epithelial stem cells may be endowed with a protective mechanism that results in cell senescence upon the persistent stimulation of proliferative pathways that activate mTOR, ultimately suppressing tumor formation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Increased mTOR activity can cause certain cells to undergo differentiation or senescence, thereby exiting the proliferative cell pool.
“increased mTOR activity can also cause certain cells to undergo differentiation or senescence, thereby exiting the proliferative cell pool (Castilho et al., 2009; Chen et al., 2008; Lee et al., 2010; Liu et al., 2007; Zhang et al., 2006; reviewed in Iglesias-Bartolome and Gutkind, 2011).”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Castilho et al., 2009
Persistent activation of mTOR by Wnt1 leads to accelerated epithelial stem cell senescence and premature aging in mice.
“we have recently shown that the persistent activation of mTOR by Wnt1 leads to accelerated epithelial stem cell senescence and premature aging in mice (Castilho et al., 2009; Liu et al., 2007)”
From mTOR inhibition prevents epithelial stem cell senescence and protects from radiation-induced mucositis (2012) · cites this paper as Castilho et al., 2009
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 56 · Cited by 371
- Authors
- Castilho, R. M., Squarize, C. H., Chodosh, L. A., Williams, B. O., & Gutkind, J. S.
- Affiliations
- National Institutes of Health (US)
- University of Pennsylvania (US)
- Van Andel Institute (US)
- Corresponding author
- Gutkind, J. Silvio
- Venue
- Cell stem cell
- Publisher
- Elsevier BV
- Published
- 2009-09
- Volume
- 5
- Issue
- 3
- Pages
- 279-289
- ISSN
- 1875-9777 (ISSN-L)
- 1934-5909
- PMC
- PMC2939833
- OpenAlex
- W1990928498
- Cited by
- 371
- References
- 56
- Citations by year
- 2026: 3 · 2025: 14 · 2024: 9 · 2023: 17 · 2022: 21 · 2021: 17 · 2020: 23 · 2019: 21 · 2018: 27 · 2017: 27 · 2016: 24 · 2015: 29 · 2014: 29 · 2013: 27 · 2012: 36
- FWCI
- 32.08
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell stem cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health
- National Institute of Dental and Craniofacial Research (Z01DE000558)
- Topics
- Health Sciences › Medicine › Urology › Hair Growth and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Wnt/β-catenin signaling in development and cancer
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Keywords
- mTOR, Wnt signaling, Wnt1, epidermal stem cells, stem cell exhaustion, aging, β-catenin, hair loss, tumor suppression, stem cell niche
- MeSH terms
- Epidermal Cells, Animals, Cell Separation, Doxycycline, Epithelial Cells, Protein Kinases, Regeneration, Stem Cells, Signal Transduction, Keratinocytes, Cellular Senescence, Hair Follicle, Antigens, CD34, Sirolimus, Cell Proliferation, Wnt Proteins, beta Catenin, Mice, TOR Serine-Threonine Kinases
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
