ArticleThe Journal of biological chemistry2010
Immunosuppressive cyclosporin A activates AKT in keratinocytes through PTEN suppression: implications in skin carcinogenesis.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers, 2 of them syntheses that pooled it.
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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
39 citing papers in PubMed, 2 syntheses or guidelines pooled it, 65 citations in OpenAlex.
- Sirolimus for Secondary Prevention of Cutaneous Squamous Cell Carcinoma in Kidney Transplant Recipients: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.International journal of dermatology · 2026Pooled it
- Safety and efficacy of umbilical cord-derived stem cell therapy for the treatment of cerebral palsy patients: a systematic review.Orphanet journal of rare diseases · 2025Pooled it
- Umbilical cord blood therapy potentiated with erythropoietin for children with cerebral palsy: a double-blind, randomized, placebo-controlled trial.Stem cells (Dayton, Ohio) · 2013Trial
- Trial
- Autophagy regulates tumor growth and metastasis.bioRxiv : the preprint server for biology · 2023Article
- Use of Systemic Therapies for Treatment of Psoriasis in Patients with a History of Treated Solid Tumours: Inference-Based Guidance from a Multidisciplinary Expert Panel.Dermatology and therapy · 2023Article
- Decoding the Phosphatase Code: Regulation of Cell Proliferation by Calcineurin.International journal of molecular sciences · 2022Review
- Current Trends and Characteristics of Hepatocellular Carcinoma in Patients with Autoimmune Liver Diseases.Cancers · 2021Review
- Case Report: Combined Intra-Lesional IL-2 and Topical Imiquimod Safely and Effectively Clears Multi-Focal, High Grade Cutaneous Squamous Cell Cancer in a Combined Liver and Kidney Transplant Patient.Frontiers in immunology · 2021Review
- Cutaneous Squamous Cell Carcinoma: From Biology to Therapy.International journal of molecular sciences · 2020Review
- Unraveling cancer lineage drivers in squamous cell carcinomas.Pharmacology & therapeutics · 2020Review
- Cyclosporin A aggravates hydrogen peroxide-induced cell death in kidney proximal tubule epithelial cells.Anatomy & cell biology · 2019Article
- Therapeutic Chemical Screen Identifies Phosphatase Inhibitors to Reconstitute PKB Phosphorylation and Cardiac Contractility in ILK-Deficient Zebrafish.Biomolecules · 2018Article
- Merkel cell carcinoma: Epidemiology, pathogenesis, diagnosis and therapy.Reviews in endocrine & metabolic disorders · 2017Review
- Epidermal SIRT1 regulates inflammation, cell migration, and wound healing.Scientific reports · 2017Article
- Honokiol inhibits c-Met-HO-1 tumor-promoting pathway and its cross-talk with calcineurin inhibitor-mediated renal cancer growth.Scientific reports · 2017Article
- Arsenic Induces p62 Expression to Form a Positive Feedback Loop with Nrf2 in Human Epidermal Keratinocytes: Implications for Preventing Arsenic-Induced Skin Cancer.Molecules (Basel, Switzerland) · 2017Article
- Distinct Role of Sesn2 in Response to UVB-Induced DNA Damage and UVA-Induced Oxidative Stress in Melanocytes.Photochemistry and photobiology · 2017Article
- High expression of Sam68 in sacral chordomas is associated with worse clinical outcomes.OncoTargets and therapy · 2017Article
- Autophagy gene ATG7 regulates ultraviolet radiation-induced inflammation and skin tumorigenesis.Autophagy · 2017Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Non-melanoma skin cancer, the most common neoplasia after solid organ transplantation, causes serious morbidity and mortality and is related to sun exposure. Cyclosporin A (CsA) has been used widely to prevent rejection in organ transplantation. The mechanism of CsA action in causing cancer was thought to be well understood via immunosuppression. Here, we show that CsA promotes primary skin tumor growth in immune-deficient mice and keratinocyte growth in vitro. In addition, CsA enhances keratinocyte survival from removal of extracellular matrix or UVB radiation. At the molecular level, CsA increases AKT activation after serum treatment and UVB irradiation. Furthermore we found that expression of PTEN, the negative regulator of AKT activation, is significantly reduced post-CsA in human HaCaT and A431 cells and in mouse skin in vivo. CsA-induced PTEN down-regulation occurs at the transcription level and is epidermal growth factor receptor-dependent. Such PTEN suppression is required for increased AKT activation. Inhibition of AKT activation abolishes CsA-promoted growth and survival, indicating that AKT hyperactivation is essential for both growth and survival of CsA-treated cells. In addition, mTOR signaling as a known AKT downstream pathway is required for CsA-enhanced growth and survival. Taken together, we have identified the PTEN/AKT pathway as new molecular targets of CsA in epidermal keratinocytes, suggesting a previously unknown mechanism in CsA-enhanced skin carcinogenesis. Our findings challenge assumptions about how CsA-associated tumors arise in skin.
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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.