ArticleOncotarget2015
PI3K/AKT/mTOR pathway plays a major pathogenetic role in glycogen accumulation and tumor development in renal distal tubules of rats and men.
Article in Oncotarget, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 54 citations in OpenAlex.
- Natural Products in Clear Cell Renal Cell Carcinoma: Rewiring the VHL-HIF Axis, Metabolic Plasticity, and Tumor-Immune Interactions.International journal of molecular sciences · 2026Review
- Identification and Validation of a Prognostic Model Based on Tumour Necrosis Factor-Related mRNAs for Kidney Renal Clear Cell Carcinoma.Journal of cellular and molecular medicine · 2025Article
- Identification and Validation of a Prognostic Signature Based on mRNAs Associated with Low-Density Lipoprotein Receptor-Related Proteins for Kidney Renal Clear Cell Carcinoma: Insights Into Tumor Immune Microenvironment, Mutation Patterns, and Personalized Treatment Strategies.International journal of general medicine · 2025Article
- Hyperbaric oxygen therapy prevents epithelial atrophy in distal tubules and TGF-β1 overexpression in diabetic rat kidneys.Journal of molecular histology · 2024Article
- Knockout of the Carbohydrate Responsive Element Binding Protein Enhances Proliferation and Tumorigenesis in Renal Tubules of Mice.International journal of molecular sciences · 2024Article
- The Influence of Soy Isoflavones and Soy Isoflavones with Inulin on Kidney Morphology, Fatty Acids, and Associated Parameters in Rats with and without Induced Diabetes Type 2.International journal of molecular sciences · 2024Article
- Rational combination platform trial design for children and young adults with diffuse midline glioma: A report from PNOC.Neuro-oncology · 2024Article
- Mechanisms and efficacy of traditional Chinese herb monomers in diabetic kidney disease.International urology and nephrology · 2024Review
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- Overexpression of cytoplasmic dynamin 2 is associated with worse outcomes in patients with clear cell renal cell carcinoma.Cancer biomarkers : section A of Disease markers · 2022Article
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- Exploring the mechanisms underlying the therapeutic effect of Salvia miltiorrhiza in diabetic nephropathy using network pharmacology and molecular docking.Bioscience reports · 2021Article
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- Network Pharmacology Combined with Bioinformatics to Investigate the Mechanisms and Molecular Targets ofEvidence-based complementary and alternative medicine : eCAM · 2021Article
- Review
- Transcriptomic and Proteomic Analysis of Clear Cell Foci (CCF) in the Human Non-Cirrhotic Liver Identifies Several Differentially Expressed Genes and Proteins with Functions in Cancer Cell Biology and Glycogen Metabolism.Molecules (Basel, Switzerland) · 2020Article
- Evaluation of the prognostic role of co-morbidities on disease outcome in renal cell carcinoma patients.World journal of urology · 2020Article
- Dysregulated metabolic pathways in age-related macular degeneration.Scientific reports · 2020Article
- Modulation of Calcium Homeostasis May Be Associated with Susceptibility to Renal Cell Carcinoma in Diabetic Nephropathy Rats.Cancer management and research · 2020Article
- Does diabetes mellitus play an independent prognostic role in kidney cancer?Annals of translational medicine · 2019Article
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the PI3K/AKT/mTOR pathway is a crucial molecular event in human clear cell renal cell carcinoma (ccRCC), and is also upregulated in diabetic nephropathy. In diabetic rats metabolic changes affect the renal distal tubular epithelium and lead to glycogen-storing Armanni-Ebstein lesions (AEL), precursor lesions of RCC in the diabetes induced nephrocarcinogenesis model. These lesions resemble human sporadic clear cell tubules (CCT) and tumor cells of human ccRCC.Human sporadic CCT were examined in a collection of 324 nephrectomy specimen, in terms of morphologic, metabolic and molecular alterations, and compared to preneoplastic CCT and RCC developed in the rat following streptozotocin-induced diabetes or N-Nitrosomorpholine administration. Diabetic and non-diabetic rats were subjected to the dual PI3K/mTOR inhibitor, NVP/BEZ235.Human sporadic CCT could be detected in 17.3% of kidney specimens. Human and rat renal CCT display a strong induction of the PI3K/AKT/mTOR pathway and related metabolic alterations. Proteins involved in glycolysis and de novo lipogenesis were upregulated. In in vivo experiments, dual inhibition of PI3K and mTOR resulted in a reduction of proliferation of rat diabetes related CCT and increased autophagic activity.The present data indicate that human sporadic CCT exhibit a pattern of morphologic and metabolic alterations similar to preneoplastic lesions in the rat model. Activation of the PI3K/AKT/mTOR pathway in glycogenotic tubuli is a remarkable molecular event and suggests a preneoplastic character of these lesions also in humans.
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