ArticleEBioMedicine2019
Cytosolic 5'-nucleotidase 1A is overexpressed in pancreatic cancer and mediates gemcitabine resistance by reducing intracellular gemcitabine metabolites.
Article in EBioMedicine, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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18 citing papers in PubMed, 41 citations in OpenAlex.
- Ploidy shapes gemcitabine response through altered potency and delayed cell death.bioRxiv : the preprint server for biology · 2026Article
- Role and molecular mechanisms of hypoxia-derived exosomal miR-301a on gemcitabine resistance in pancreatic cancer.Oncology letters · 2025Article
- A novel cuproptosis-related genes nomogram on the prognosis and immune microenvironment of breast invasive carcinoma.Scientific reports · 2025Article
- Article
- Development of a novel risk signature revealing prognostic and tumor microenvironmental features in breast cancer.Medicine · 2025Article
- Barriers and opportunities for gemcitabine in pancreatic cancer therapy.American journal of physiology. Cell physiology · 2023Review
- Vibrational spectroscopy - are we close to finding a solution for early pancreatic cancer diagnosis?World journal of gastroenterology · 2023Review
- Axon guidance receptor ROBO3 modulates subtype identity and prognosis via AXL-associated inflammatory network in pancreatic cancer.JCI insight · 2022Article
- Resistance to Gemcitabine in Pancreatic Ductal Adenocarcinoma: A Physiopathologic and Pharmacologic Review.Cancers · 2022Review
- Substrate-Based Design of Cytosolic Nucleotidase IIIB Inhibitors and Structural Insights into Inhibition Mechanism.Pharmaceuticals (Basel, Switzerland) · 2022Article
- TNF-α-producing macrophages determine subtype identity and prognosis via AP1 enhancer reprogramming in pancreatic cancer.Nature cancer · 2021Article
- Review
- Stellate Cells Aid Growth-Permissive Metabolic Reprogramming and Promote Gemcitabine Chemoresistance in Pancreatic Cancer.Cancers · 2021Review
- The Current Treatment Paradigm for Pancreatic Ductal Adenocarcinoma and Barriers to Therapeutic Efficacy.Frontiers in oncology · 2021Review
- Article
- Co-targeting of CXCR4 and hedgehog pathways disrupts tumor-stromal crosstalk and improves chemotherapeutic efficacy in pancreatic cancer.The Journal of biological chemistry · 2020Article
- Article
- Drug resistance in pancreatic cancer: New player caught in act.EBioMedicine · 2019Article
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Authors and funding
18 authors at 2 institutions in 2 countries.
Funding
Abstract
backgroundCytosolic 5'-nucleotidase 1A (NT5C1A) dephosphorylates non-cyclic nucleoside monophosphates to produce nucleosides and inorganic phosphates. Here, we investigate NT5C1A expression in pancreatic ductal adenocarcinoma (PDAC) and its impact on gemcitabine metabolism and therapeutic efficacy.
methodsNT5C1A expression was determined by semiquantitative immunohistochemistry using tissue microarrays. Gemcitabine metabolites and response were assessed in several human and murine PDAC cell lines using crystal violet assays, Western blot, viability assays, and liquid chromatography tandem mass-spectrometry (LC-MS/MS).
findingsNT5C1A was strongly expressed in tumor cells of a large subgroup of resected PDAC patients in two independent patient cohorts (44-56% score 2 and 8-26% score 3, n = 414). In contrast, NT5C1A was expressed at very low levels in the tumor stroma, and neither stromal nor tumoral expression was a prognostic marker for postoperative survival. In vitro, NT5C1A overexpression increased gemcitabine resistance by reducing apoptosis levels and significantly decreased intracellular amounts of cytotoxic dFdCTP in +NT5C1A tumor cells. Co-culture experiments with conditioned media from +NT5C1A PSCs improved gemcitabine efficacy in tumor cells. In vivo, therapeutic efficacy of gemcitabine was significantly decreased and serum levels of the inactive gemcitabine metabolite dFdU significantly increased in mice bearing NT5C1A overexpressing tumors.
interpretationNT5C1A is robustly expressed in tumor cells of resected PDAC patients. Moreover, NT5C1A mediates gemcitabine resistance by decreasing the amount of intracellular dFdCTP, leading to reduced tumor cell apoptosis and larger pancreatic tumors in mice. Further studies should clarify the role of NT5C1A as novel predictor for gemcitabine treatment response in patients with PDAC.
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