Mitochondrial Calcium Uniporter Drives Chemoresistance in Pancreatic Cancer via Glutathione-Mediated Stemness Maintenance.
1/5 보강
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with poor prognosis due to chemoresistance.
APA
Li Z, Meng C, et al. (2026). Mitochondrial Calcium Uniporter Drives Chemoresistance in Pancreatic Cancer via Glutathione-Mediated Stemness Maintenance.. Advanced science (Weinheim, Baden-Wurttemberg, Germany), 13(17), e07346. https://doi.org/10.1002/advs.202507346
MLA
Li Z, et al.. "Mitochondrial Calcium Uniporter Drives Chemoresistance in Pancreatic Cancer via Glutathione-Mediated Stemness Maintenance.." Advanced science (Weinheim, Baden-Wurttemberg, Germany), vol. 13, no. 17, 2026, pp. e07346.
PMID
41560687 ↗
Abstract 한글 요약
Pancreatic ductal adenocarcinoma (PDAC) remains a lethal malignancy with poor prognosis due to chemoresistance. Using integrative single-cell RNA sequencing, we identified that the upregulation of mitochondrial calcium uniporter (MCU) may contribute to chemoresistance and stemness maintenance in PDAC. MCU was highly expressed in chemotherapy-resistant PDAC tumors and correlated with enhanced cancer stem cell properties. Mechanistically, MCU-mediated mitochondrial Ca influx triggered endoplasmic reticulum (ER) stress and the downstream PERK-eIF2α pathway. This cascade activated ATF4 and NRF2, which enhanced the transcriptional regulation of PSAT1 and SLC7A11. These changes promoted de novo glutathione (GSH) synthesis to scavenge reactive oxygen species (ROS) and sustain stemness. Genetic knockdown or pharmacological inhibition of MCU disrupted GSH synthesis, suppressed stemness, and restored sensitivity to nab-paclitaxel plus gemcitabine (AG). High-throughput screening identified MCU inhibitor NB-598, which synergized with AG to inhibit tumor growth in preclinical models. These findings offer a potential novel therapeutic strategy to address chemoresistance in PDAC.
🏷️ 키워드 / MeSH 📖 같은 키워드 OA만
- Humans
- Pancreatic Neoplasms
- Drug Resistance
- Neoplasm
- Neoplastic Stem Cells
- Glutathione
- Carcinoma
- Pancreatic Ductal
- Calcium Channels
- Animals
- Mice
- Cell Line
- Tumor
- Endoplasmic Reticulum Stress
- Gemcitabine
- Reactive Oxygen Species
- Mitochondria
- Deoxycytidine
- chemoresistance
- glutathione synthesis
- mitochondrial calcium uniporter
- pancreatic ductal adenocarcinoma
- stemness maintenance
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