ArticleJournal of translational medicine2024
SLC38A5 suppresses ferroptosis through glutamine-mediated activation of the PI3K/AKT/mTOR signaling in osteosarcoma.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed.
- Unraveling the role of glutamine metabolism in cancer: from cell death mechanisms to tumor microenvironment modulation.Experimental hematology & oncology · 2026Review
- Intestinal Epithelial Cell Ferroptosis in Ulcerative Colitis: Pathogenesis, Signaling Networks, and Therapeutic Implications.Current medical science · 2026Review
- The crosslink between autophagy and ferroptosis in polycystic ovary syndrome: from synergistic pathogenesis to targeted therapy.Journal of ovarian research · 2026Review
- BCAT1 inhibits glutamine-dependent Akt/mTOR signaling and nucleotide synthesis by initiating BTRC-mediated degradation of SLC3A2 in pancreatic adenocarcinoma.Cancer & metabolism · 2026Article
- Targeting Ferroptosis With Natural Products for the Treatment of Skeletal System Disease: An Updated Review.Journal of cellular and molecular medicine · 2026Review
- Research Progress on the Physiological Functions of Aspartic Acid and Its Applications in Animal Production.Animals : an open access journal from MDPI · 2026Review
- The protective up-regulation of metallothionein-2A in intervertebral disc degeneration inhibits nucleus pulposus cell ferroptosis through activation of the PI3K/AKT/mTOR pathway.Cell death discovery · 2026Article
- Metabolic-immune crosstalk in osteosarcoma: mechanisms and therapeutic opportunities.Frontiers in immunology · 2026Review
- Natural products reshape osteosarcoma cell fate: promoting cell death.Frontiers in pharmacology · 2026Review
- An Epithelial-Mesenchymal Transition-Driven Transcriptional Index Stratifies Immunosuppression and Therapeutic Resistance in Bone Malignancies.International journal of genomics · 2026Article
- Integrative biomarker and drug target discovery in osteosarcoma: traditional experimental approaches and AI-enabled insights.Frontiers in pharmacology · 2026Review
- Impaired redox adaptation through SLC38A5-dependent glutamine metabolism contributes to melatonin-mediated anoikis sensitivity and metastasis suppression in bone cancer.International journal of biological sciences · 2026Article
- [Glutamine metabolic reprogramming in regulating the occurrence and development of osteosarcoma].Zhong nan da xue xue bao. Yi xue ban = Journal of Central South University. Medical sciences · 2025Review
- Time-restricted feeding protects against septic liver injury by reshaping gut microbiota and metabolite 3-hydroxybutyrate.Gut microbes · 2025Article
- Integrative Single-Cell and Machine Learning Analysis Develops a Glutamine Metabolism-Based Prognostic Model and Identifies MSMO1 as a Therapeutic Target in Osteosarcoma.Biomolecules · 2025Article
- TWF2 Drives Tumor Progression and Sunitinib Resistance in Renal Cell Carcinoma through Hippo Signaling Suppression.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Integrated multi-omics analysis reveals AKR1C1 as a key mediator of intervertebral disc degeneration: protecting against ferroptosis via PI3K/AKT signaling.Functional & integrative genomics · 2025Article
- Polygonum multiflorum Stilbene Glycoside Oligomers induce the ferroptosis of triple negative breast cancer cells.BMC cancer · 2025Article
- Cancer-associated Fibroblast-like Cells Promote Osteosarcoma Metastasis by Upregulation of Phosphoserine Aminotransferase 1 and Activation of the mTOR/S6K Pathway.International journal of biological sciences · 2025Article
- SOX2 induces LPCAT1 expression to promote cholesterol metabolic reprogramming-mediated invasion and metastasis in osteosarcoma.Frontiers in molecular biosciences · 2025Article
Corrections and comments
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Authors and funding
6 authors.
Funding
Abstract
backgroundSolute carrier family 38 member 5 (SLC38A5) is an amino acid transporter that plays a significant role in various cellular biological processes and may be involved in regulating the progression of tumors However, its function and underlying mechanism in osteosarcoma remain unexplored.
methodsUtilizing various database analyses and experiments, we have explored the dysregulation of SLC38A5 in osteosarcoma and its prognostic value. A series of in vitro functional experiments, including CCK-8, colony formation, wound healing, and transwell invasion assays, were conducted to evaluate the effects of SLC38A5 on the proliferation, migration, and invasion of osteosarcoma cells. Downstream pathways of SLC38A5 were explored through methods such as western blot and metabolic assays, followed by a series of validations. Finally, we constructed a subcutaneous xenograft tumor model in nude mice to explore SLC38A5 function in vivo.
resultsSLC38A5 is upregulated in osteosarcoma and is associated with poor prognosis in patients. Upregulation of SLC38A5 promotes proliferation, migration, and invasion of osteosarcoma cells, while the PI3K inhibitor BKM120 can counteract these effects. Additionally, silencing of SLC38A5 inhibits tumor growth in vivo. Mechanistically, SLC38A5 mediates the activation of the PI3K/AKT/mTOR signaling pathway by transporting glutamine, which subsequently enhances the SREBP1/SCD-1 signaling pathway, thereby suppressing ferroptosis in osteosarcoma cells.
conclusionSLC38A5 promotes osteosarcoma cell proliferation, migration, and invasion via the glutamine-mediated PI3K/AKT/mTOR signaling pathway and inhibits ferroptosis. Targeting SLC38A5 and the PI3K/AKT signaling axis may provide a meaningful therapeutic strategy for the future treatment of osteosarcoma.
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