ArticleCancer medicine2023
SLC12A5 promotes hepatocellular carcinoma growth and ferroptosis resistance by inducing ER stress and cystine transport changes.
Article in Cancer medicine, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 31 citations in OpenAlex.
- The Mechanism of Long Non-coding RNA GABPB1-AS1/SLC12A5 Regulating Neuronal Ferroptosis in Epileptic Seizures.Neurochemical research · 2026Article
- Intestinal Epithelial Cell Ferroptosis in Ulcerative Colitis: Pathogenesis, Signaling Networks, and Therapeutic Implications.Current medical science · 2026Review
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
- Therapeutic potential of diosgenin in hepatocellular carcinoma through molecular mechanisms and nanodelivery strategies.Discover oncology · 2026Review
- Unraveling the role of the solute carrier family in hepatocellular carcinoma: mechanisms and therapeutic prospects.Cancer cell international · 2025Review
- Family History of Hypertension Predicts Thyroid Cancer Risk in Women: A Population-Based Cross-Sectional Study With Integrative Machine Learning and Genomic Analyses.Cancer medicine · 2025Article
- Patient-derived xenograft model: Applications and challenges in liver cancer.Chinese medical journal · 2025Review
- Association between blood pressure traits, hypertension, antihypertensive drugs and calcific aortic valve stenosis: a mendelian randomization study.Journal of geriatric cardiology : JGC · 2025Article
- Role of solute carrier transporters in ovarian cancer (Review).International journal of molecular medicine · 2025Review
- Prenatal opioid exposure alters pain perception and increases long-term health risks in infants with neonatal opioid withdrawal syndrome.Frontiers in pain research (Lausanne, Switzerland) · 2025Article
- ETV4‑mediated transcriptional activation of SLC12A5 exacerbates ferroptosis resistance and glucose metabolism reprogramming in breast cancer cells.Molecular medicine reports · 2024Article
- Unveiling the therapeutic potential of IHMT-337 in glioma treatment: targeting the EZH2-SLC12A5 axis.Molecular medicine (Cambridge, Mass.) · 2024Article
- Borax affects cellular viability by inducing ER stress in hepatocellular carcinoma cells by targeting SLC12A5.Journal of cellular and molecular medicine · 2024Article
- Ferroptosis resistance in cancer cells: nanoparticles for combination therapy as a solution.Frontiers in pharmacology · 2024Review
- SLC12A5 promotes hepatocellular carcinoma growth and ferroptosis resistance by inducing ER stress and cystine transport changes.Cancer medicine · 2023Article
- Iron accumulation and lipid peroxidation: implication of ferroptosis in hepatocellular carcinoma.Frontiers in endocrinology · 2023Review
- Neutrophil-Derived IL-6 Potentially Drives Ferroptosis Resistance in B Cells in Lupus Kidney.Mediators of inflammation · 2023Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundHepatocellular carcinoma (HCC) has a poor prognosis and new effective treatments are needed. SLC12A5 plays important roles in multiple complex pathological states and is overexpressed in a variety of malignancies. However, the effects of SLC12A5 in HCC have not been determined.
methodsSLC12A5 expression was assessed by immunostaining and western blotting. A cell viability assay was used to detect cell proliferation. Flow cytometry was used to evaluate the intracellular calcium concentration and cell cycle. Ferroptosis was detected by transmission electron microscopy, lipid peroxidation, and glutathione assays. Subcutaneous tumor formation experiments were used to validate the tumorigenic effect of SLC12A5 in vivo. RNA-seq was used to evaluate the molecular mechanisms underlying the effects of SLC12A5. The therapeutic efficacy of targeting SLC12A5 was assessed in a patient-derived xenograft (PDX) model.
resultsHigh SLC12A5 expression was strongly associated with a poor clinical prognosis and promoted HCC growth. Mechanistically, SLC12A5 promoted ER stress to enhance calcium release and upregulated PNCK expression levels. Concomitantly, PNCK was significantly activated by calcium ions released from the ER. PNCK activated and induced the phosphorylation of PI3K/AKT/mTOR pathway components. Furthermore, SLC12A5 inhibited ferroptosis in HCC by upregulating the expression of xCT, a cystine transporter.
conclusionHigh SLC12A5 levels were correlated with a poor prognosis, promoted tumorigenesis, and inhibited ferroptosis in HCC. These findings suggested that SLC12A5 is a therapeutic target and provide insight into the link between ER stress and ferroptosis in HCC.
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