ArticleCell death and differentiation2017
Rictor/mTORC2 deficiency enhances keratinocyte stress tolerance via mitohormesis.
Article in Cell death and differentiation, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 26 citations in OpenAlex.
- Ankyloblepharon-Ectodermal Defects-Cleft Lip/Palate Syndrome-Linked p63 Mutations Disrupt Keratinocyte Proliferation and Survival Through Oxidative Stress and Impaired Slc7a11 Expression.International journal of molecular sciences · 2025Article
- RICTOR/mTORC2 downregulation in BRAFMolecular cancer · 2024Article
- mTORC2 Is Activated under Hypoxia and Could Support Chronic Myeloid Leukemia Stem Cells.International journal of molecular sciences · 2023Article
- NAD/NAMPT and mTOR Pathways in Melanoma: Drivers of Drug Resistance and Prospective Therapeutic Targets.International journal of molecular sciences · 2022Review
- Mitochondrial ROS drive resistance to chemotherapy and immune-killing in hypoxic non-small cell lung cancer.Journal of experimental & clinical cancer research : CR · 2022Article
- Review
- Review
- 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
- Multifunctional thiosemicarbazones targeting sigma receptors: in vitro and in vivo antitumor activities in pancreatic cancer models.Cellular oncology (Dordrecht, Netherlands) · 2021Article
- Tumor-Associated Antigen xCT and Mutant-p53 as Molecular Targets for New Combinatorial Antitumor Strategies.Cells · 2021Review
- NAMPT Over-Expression Recapitulates the BRAF Inhibitor Resistant Phenotype Plasticity in Melanoma.Cancers · 2020Article
- Sublethal exposure of small few-layer graphene promotes metabolic alterations in human skin cells.Scientific reports · 2020Article
- Influence of Long-Term Fasting on Blood Redox Status in Humans.Antioxidants (Basel, Switzerland) · 2020Article
- Shedding Light on the Effects of Calorie Restriction and its Mimetics on Skin Biology.Nutrients · 2020Review
- Loss of GCN5L1 in cardiac cells disrupts glucose metabolism and promotes cell death via reduced Akt/mTORC2 signaling.The Biochemical journal · 2019Article
- Loss ofFrontiers in immunology · 2018Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
How metabolic pathways required for epidermal tissue growth and remodeling influence the ability of keratinocytes to survive stressful conditions is still largely unknown. The mechanistic target of rapamycin complex 2 (mTORC2) regulates growth and metabolism of several tissues, but its functions in epidermal cells are poorly defined. Rictor is an adaptor protein essential for mTORC2 activity. To explore the roles of mTORC2 in the epidermis, we have conditionally deleted rictor in mice via K14-Cre-mediated homologous recombination and found that its deficiency causes moderate tissue hypoplasia, reduced keratinocyte proliferation and attenuated hyperplastic response to TPA. Noteworthy, rictor-deficient keratinocytes displayed increased lifespan, protection from senescence, and enhanced tolerance to cellular stressors such as growth factors deprivation, epirubicin and X-ray in vitro and radioresistance in vivo. Rictor-deficient keratinocytes exhibited changes in global gene expression profiles consistent with metabolic alterations and enhanced stress tolerance, a shift in cell catabolic processes from glycids and lipids to glutamine consumption and increased production of mitochondrial reactive oxygen species (ROS). Mechanistically, the resiliency of rictor-deficient epidermal cells relies on these ROS increases, indicating stress resistance via mitohormesis. Thus, our findings reveal a new link between metabolic changes and stress adaptation of keratinocytes centered on mTORC2 activity, with potential implications in skin aging and therapeutic resistance of epithelial tumors.
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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.