ArticleAutophagy2019
AKT inhibition-mediated dephosphorylation of TFE3 promotes overactive autophagy independent of MTORC1 in cadmium-exposed bone mesenchymal stem cells.
Article in Autophagy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 66 citations in OpenAlex.
- The Protective Mechanism of Continuous Theta Burst Stimulation in the Acute Phase of Stroke Through Modulation of the Calcineurin/AKT/FOXO1 Signaling Pathway.CNS neuroscience & therapeutics · 2026Article
- Single and combined nanotoxicity of titanium dioxide and cadmium: implications for skeletal and behavioral development in zebrafish.Environmental science and pollution research international · 2026Article
- Modulation of the PI3K/AKT/mTOR and AMPK/TSC2/mTOR Pathways by N-Acetyl-L-Cysteine as a Protector of Embryonic Bodies from the Toxic Effect of Methylmercury.Brain sciences · 2026Review
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- OR2T6 modulates autophagy through the PPP3CA-mediated pathways to suppress gastric cancer.Cell death and differentiation · 2026Article
- Cadmium disrupts hepatic lipid homeostasis: molecular mechanisms, unresolved controversies, and therapeutic strategies.iScience · 2026Review
- Targeting mitochondrial damage and ER stress to inhibit ferroptosis in cadmium-induced nephrotoxicity.Toxicology reports · 2025Review
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- Article
- SIRT5-Mediated Desuccinylation of RAB7A Protects Against Cadmium-Induced Alzheimer's Disease-Like Pathology by Restoring Autophagic Flux.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Blockage of Akt activation suppresses cadmium-induced renal tubular cellular damages through aggrephagy in HK-2 cells.Scientific reports · 2024Article
- Luteolin Alleviates Cadmium-Induced Kidney Injury by Inhibiting Oxidative DNA Damage and Repairing Autophagic Flux Blockade in Chickens.Antioxidants (Basel, Switzerland) · 2024Article
- Cadmium-induced annulus fibrosus cell senescence contributes to intervertebral disc degeneration via the JNK/p53 signaling pathway.Iranian journal of basic medical sciences · 2024Article
- Recent insights into autophagy and metals/nanoparticles exposure.Toxicological research · 2023Review
- Chelerythrine-Induced Apoptotic Cell Death in HepG2 Cells Involves the Inhibition of Akt Pathway and the Activation of Oxidative Stress and Mitochondrial Apoptotic Pathway.Antioxidants (Basel, Switzerland) · 2022Article
- Article
- Non-enzymatic heparanase enhances gastric tumor proliferation via TFEB-dependent autophagy.Oncogenesis · 2022Article
- Autophagy enhanced by curcumin ameliorates inflammation in atherogenesisActa pharmaceutica Sinica. B · 2022Article
- NUPR1 promotes the proliferation and metastasis of oral squamous cell carcinoma cells by activating TFE3-dependent autophagy.Signal transduction and targeted therapy · 2022Article
- The mucin protein MUCL1 regulates melanogenesis and melanoma genes in a manner dependent on threonine content.The British journal of dermatology · 2022Article
Corrections and comments
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Authors and funding
22 authors at 7 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Cadmium (Cd) is a toxic metal that is widely found in numerous environmental matrices and induces serious adverse effects in various organs and tissues. Bone tissue seems to be a crucial target of Cd contamination. Macroautophagy/autophagy has been proposed to play a pivotal role in Cd-mediated bone toxicity. However, the mechanisms that underlie Cd-induced autophagy are not yet completely understood. We demonstrated that Cd treatment increased autophagic flux and inhibition of the autophagic process using Atg7 gene silencing blocked the Cd-induced mesenchymal stem cell death. Mechanistically, Cd activated nuclear translocation of TFE3 but not that of TFEB or MITF, which contributed to the expression of autophagy-related genes and lysosomal biogenesis. Specifically, Cd decreased expression of phospho-AKT (Ser473). The reduction in AKT activity led to dephosphorylation of cytosolic TFE3 at Ser565 and promoted TFE3 nuclear translocation independently of MTORC1. Notably, Cd treatment increased the activity of PPP3/calcineurin, and pharmacological inhibition of PPP3/calcineurin with FK506 suppressed AKT dephosphorylation and TFE3 activity. These results suggest that PPP3/calcineurin negatively regulates AKT phosphorylation and is involved in Cd-induced TFE3-dependent autophagy. Modulation of the PPP3/calcineurin-AKT-TFE3 autophagic-lysosomal machinery may offer novel therapeutic approaches for the treatment of Cd-induced bone damage. Abbreviations: ACTB: actin: beta; AKT: thymoma viral proto-oncogene; AMPK: AMP-activated protein kinase; ATG: autophagy related; Baf A1: bafilomycin A
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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.