ArticleCancer research2022
Mitochondrial Calcium Uniporter Drives Metastasis and Confers a Targetable Cystine Dependency in Pancreatic Cancer.
Article in Cancer research, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers, 1 of them a synthesis that pooled it.
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Who cites it
65 citing papers in PubMed, 1 synthesis or guideline pooled it, 101 citations in OpenAlex.
- Knowledge mapping of mitochondrial calcium uniporter from 2011 to 2022: A bibliometric analysis.Frontiers in physiology · 2023Pooled it
- Platelet-derived mitochondrial transfer in cancer metastasis: mechanisms, functional consequences, and translational opportunities.Clinical & experimental metastasis · 2026Review
- Article
- Electrical Signals at the Subcellular Scale: How Electroactive Materials Regulate Stem Cell Fate.Advanced materials (Deerfield Beach, Fla.) · 2026Review
- Integrated Bioinformatics and Experimental Validation Reveal the Diagnostic and Prognostic Value of SMDT1 in Thyroid Carcinoma.Diagnostics (Basel, Switzerland) · 2026Article
- Coenzyme A mitigates cystine-deprivation-induced ferroptosis by suppressing the iron-starvation response.The FEBS journal · 2026Article
- Mitophagy and Ubiquitination Coordinate Context-Specific Mitochondrial Quality Control and EMT/MET Plasticity to Drive Cancer Cell Invasion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Mitochondrial Calcium Uniporter Drives Chemoresistance in Pancreatic Cancer via Glutathione-Mediated Stemness Maintenance.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Navigating the complexities of ferroptosis in pancreatic ductal adenocarcinoma: roles, mechanisms and potential applications.Cell death discovery · 2026Review
- Article
- Ferroptosis in cancer toward molecular insights and clinical translation in pancreatic cancer.Molecular cancer · 2026Review
- Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities.Molecular cancer · 2026Review
- Mitochondrial calcium uniporter as a biomarker in lung adenocarcinoma: regulation of the immune microenvironment, apoptosis, cell cycle and mitophagy.American journal of cancer research · 2026Article
- Adaptation to cystine limitation stress confers a targetable lipid metabolism vulnerability in pancreatic ductal adenocarcinoma.Nature communications · 2025Article
- Mitochondrial Glutathione Import Enables Breast Cancer Metastasis via Integrated Stress Response Signaling.Cancer discovery · 2025Article
- Rotenone inhibited osteosarcoma metastasis by modulating ZO-2 expression and location via the ROS/CaRedox report : communications in free radical research · 2025Article
- CLT-003 exerts anti-tumor activity in pancreatic cancer by blocking the PI3K/AKT/HIF-1α pathway.Cancer biology & medicine · 2025Article
- Ferroptosis in Cancer and Inflammatory Diseases: Mechanisms and Therapeutic Implications.MedComm · 2025Review
- CircCNOT6L modulates alternative splicing of SLC7A11 via splicing factor SRSF2 to confer ferroptosis resistance and promote metastasis in prostate cancer.Experimental & molecular medicine · 2025Article
- Mitochondrial CaJournal of cellular physiology · 2025Review
5 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
16 authors at 5 institutions in 2 countries.
Funding
Abstract
Pancreatic ductal adenocarcinoma (PDAC) is a highly metastatic disease with few effective treatments. Here we show that the mitochondrial calcium uniporter (MCU) promotes PDAC cell migration, invasion, metastasis, and metabolic stress resistance by activating the Keap1-Nrf2 antioxidant program. The cystine transporter SLC7A11 was identified as a druggable target downstream of the MCU-Nrf2 axis. Paradoxically, despite the increased ability to uptake cystine, MCU-overexpressing PDAC demonstrated characteristics typical of cystine-deprived cells and were hypersensitive to cystine deprivation-induced ferroptosis. Pharmacologic inhibitors of SLC7A11 effectively induced tumor regression and abrogated MCU-driven metastasis in PDAC. In patient-derived organoid models in vitro and patient-derived xenograft models in vivo, MCU-high PDAC demonstrated increased sensitivity to SLC7A11 inhibition compared with MCU-low tumors. These data suggest that MCU is able to promote resistance to metabolic stress and to drive PDAC metastasis in a cystine-dependent manner. MCU-mediated cystine addiction could be exploited as a therapeutic vulnerability to inhibit PDAC tumor growth and to prevent metastasis. SIGNIFICANCE: Elevated mitochondrial calcium uptake in PDAC promotes metastasis but exposes cystine addiction and ferroptosis sensitivity that could be targeted to improve pancreatic cancer treatment.
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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.