ArticleThe Journal of clinical investigation2017
mTORC1 loss impairs epidermal adhesion via TGF-β/Rho kinase activation.
Article in The Journal of clinical investigation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
28 citing papers in PubMed, 40 citations in OpenAlex.
- 4E-BP1 acts as a molecular rheostat balancing regenerative healing and fibrotic scarring.Experimental & molecular medicine · 2026Article
- ROCK signaling at the crossroads of redox stress, mitochondrial dynamics, and metabolic disease.Redox biology · 2026Review
- The 4E-BP1 deletion modestly mitigates mTORC1-deficient epidermal barrier defects.JID innovations : skin science from molecules to population health · 2026Article
- Canonical and emerging regulatory mechanisms of tissue remodeling: shared principles across organs and therapeutic opportunities.Frontiers in immunology · 2026Review
- SERPINB5/TGF-β signaling modulates desmoplakin membrane localization and ameliorates pemphigus vulgaris skin blistering.JCI insight · 2025Article
- Downregulation of semaphorin 4A in keratinocytes reflects the features of non-lesional psoriasis.eLife · 2024Article
- mTORC1 is required for differentiation of germline stem cells in the Drosophila melanogaster testis.PloS one · 2024Article
- Glutamine deficiency drives transforming growth factor-β signaling activation that gives rise to myofibroblastic carcinoma-associated fibroblasts.Cancer science · 2023Article
- Unbiased evaluation of rapamycin's specificity as an mTOR inhibitor.Aging cell · 2023Article
- Dysregulation of the mTOR pathway by mechlorethamine.Toxicology · 2023Article
- Automated Immunofluorescence Staining for Analysis of Mitotic Stages and Division Orientation in Brain Sections.Methods in molecular biology (Clifton, N.J.) · 2023Article
- mTORC1 signaling pathway integrates estrogen and growth factor to coordinate vaginal epithelial cells proliferation and differentiation.Cell death & disease · 2022Article
- Review
- GPNMB expression identifies TSC1/2/mTOR-associated and MiT family translocation-driven renal neoplasms.The Journal of pathology · 2022Article
- Review
- mTOR-Dependent Spine Dynamics in Autism.Frontiers in molecular neuroscience · 2022Review
- The regulation of skin homeostasis, repair and the pathogenesis of skin diseases by spatiotemporal activation of epidermal mTOR signaling.Frontiers in cell and developmental biology · 2022Review
- Fibroblast-specific activation of Rnd3 protects against cardiac remodeling in diabetic cardiomyopathy via suppression of Notch and TGF-β signaling.Theranostics · 2022Article
- The role of metabolic ecosystem in cancer progression - metabolic plasticity and mTOR hyperactivity in tumor tissues.Cancer metastasis reviews · 2021Review
- RAS induced senescence of skin keratinocytes is mediated through Rho-associated protein kinase (ROCK).Molecular carcinogenesis · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
Despite its central position in oncogenic intracellular signaling networks, the role of mTORC1 in epithelial development has not been studied extensively in vivo. Here, we have used the epidermis as a model system to elucidate the cellular effects and signaling feedback sequelae of mTORC1 loss of function in epithelial tissue. In mice with conditional epidermal loss of the mTORC1 components Rheb or Rptor, mTORC1 loss of function unexpectedly resulted in a profound skin barrier defect with epidermal abrasions, blistering, and early postnatal lethality, due to a thinned epidermis with decreased desmosomal protein expression and incomplete biochemical differentiation. In mice with mTORC1 loss of function, we found that Rho kinase (ROCK) signaling was constitutively activated, resulting in increased cytoskeletal tension and impaired cell-cell adhesion. Inhibition or silencing of ROCK1 was sufficient to rescue keratinocyte adhesion and biochemical differentiation in these mice. mTORC1 loss of function also resulted in marked feedback upregulation of upstream TGF-β signaling, triggering ROCK activity and its downstream effects on desmosomal gene expression. These findings elucidate a role for mTORC1 in the regulation of epithelial barrier formation, cytoskeletal tension, and cell adhesion, underscoring the complexity of signaling feedback following mTORC1 inhibition.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.