ArticleCells2023
SLC38A5 Modulates Ferroptosis to Overcome Gemcitabine Resistance in Pancreatic Cancer.
Article in Cells, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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The trial behind it
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Who cites it
23 citing papers in PubMed, 35 citations in OpenAlex.
- The pivotal role of SCD1 in digestive cancers: Bridging lipid metabolic reprogramming and programmed cell death (Review).International journal of oncology · 2026Review
- Stearoyl-CoA desaturase 1 integrates tissue-specific oncogenic pathways into a pan-cancer ferroptosis resistance program.Cell death & disease · 2026Review
- Stiripentol induces ER stress and pyroptosis in pancreatic cancer cells under metabolic stress by dysregulating SFAs/UFAs homeostasis.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- PDK4 acts via hippo signaling to inhibit ferroptosis and reduce gemcitabine sensitivity in pancreatic cancer.Journal of molecular histology · 2026Article
- Metabolic reprogramming in cancer: dysregulation of glucose, lipid, and amino acid pathways and therapeutic opportunities.Molecular biomedicine · 2026Review
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Targeting the NSUN2-DHODH axis reverses ferroptosis resistance and oxaliplatin resistance in colorectal cancer.Frontiers in pharmacology · 2026Article
- CUL2 confers ferroptosis resistance in pancreatic cancer by disrupting KEAP1-mediated NRF2 degradation.Cancer cell international · 2025Article
- HSPB1/KDM1 A facilitates ANXA2 expression via hypomethylated DNA promoter to inhibit ferroptosis and enhance gemcitabine resistance in pancreatic cancer.Naunyn-Schmiedeberg's archives of pharmacology · 2025Article
- The Managed Acquisition of Chemoresistance as an Informative Tool for Tumor Research.International journal of molecular sciences · 2025Review
- Loss of cadherin 17 downregulates LGR5 expression, stem cell properties and drug resistance in metastatic colorectal cancer cells.Cell death & disease · 2025Article
- O-GlcNAcylation with ubiquitination stabilizes METTL3 to promoting HMGB1 degradation to inhibit ferroptosis and enhance gemcitabine resistance in pancreatic cancer.Molecular medicine (Cambridge, Mass.) · 2025Article
- Reprogrammed immuno-metabolic environment of cancer: the driving force of ferroptosis resistance.Molecular cancer · 2025Review
- The FOXP1-ABCG2 axis promotes the proliferation of cancer stem cells and induces chemoresistance in pancreatic cancer.Cancer gene therapy · 2025Article
- SLC5A3 depletion promotes apoptosis by inducing mitochondrial dysfunction and mitophagy in gemcitabine-resistant pancreatic cancer cells.Cell death & disease · 2025Article
- Integrative single-cell RNA sequencing and bulk RNA sequencing reveals the characteristics of glutathione metabolism and protective role of GSTA4 gene in pancreatic cancer.Frontiers in immunology · 2025Article
- Targeting stromal components in pancreatic ductal adenocarcinoma: a review.Ecancermedicalscience · 2025Review
- Recent progress of ferroptosis in cancers and drug discovery.Asian journal of pharmaceutical sciences · 2024Review
- Article
Corrections and comments
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Authors and funding
10 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Pancreatic cancer is characterized by a poor prognosis, with its five-year survival rate lower than that of any other cancer type. Gemcitabine, a standard treatment for pancreatic cancer, often has poor outcomes for patients as a result of chemoresistance. Therefore, novel therapeutic targets must be identified to overcome gemcitabine resistance. Here, we found that SLC38A5, a glutamine transporter, is more highly overexpressed in gemcitabine-resistant patients than in gemcitabine-sensitive patients. Furthermore, the deletion of SLC38A5 decreased the proliferation and migration of gemcitabine-resistant PDAC cells. We also found that the inhibition of SLC38A5 triggered the ferroptosis signaling pathway via RNA sequencing. Also, silencing SLC38A5 induced mitochondrial dysfunction and reduced glutamine uptake and glutathione (GSH) levels, and downregulated the expressions of GSH-related genes NRF2 and GPX4. The blockade of glutamine uptake negatively modulated the mTOR-SREBP1-SCD1 signaling pathway. Therefore, suppression of SLC38A5 triggers ferroptosis via two pathways that regulate lipid ROS levels. Similarly, we observed that knockdown of SLC38A5 restored gemcitabine sensitivity by hindering tumor growth and metastasis in the orthotopic mouse model. Altogether, our results demonstrate that SLC38A5 could be a novel target to overcome gemcitabine resistance in PDAC therapy.
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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.