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Cysteine depletion induces pancreatic tumor ferroptosis in mice
Open accessAbstract
Ferroptotic cell death and cancer: Cell death can occur through different mechanisms, several of which are being explored as potential targets for cancer treatment. One form of cell death that has attracted recent interest is ferroptosis, which is triggered by high intracellular levels of lipid reactive oxygen species. Pancreatic cancer cells have high levels of reactive oxygen species but manage to avoid ferroptosis by importing extracellular cysteine. Studying mice bearing pancreatic tumors, Badgley et al. found that administration of a drug inhibiting cysteine import induced tumor-selective ferroptosis and inhibited tumor growth. Further work will be required to determine whether this therapeutic strategy will be effective in human pancreatic cancer, a tumor type for which new treatments are urgently needed. Science , this issue p. 85
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“Reflecting on recent reports suggesting that depletion of CoA contributes to the induction of ferroptosis by erastin (25, 26)”
From Eprenetapopt triggers ferroptosis, inhibits NFS1 cysteine desulfurase, and synergizes with serine and glycine dietary restriction (2022) · cites this paper as [25]
Experimental — accuracy not yet measuredIn the citing paper
“Labile iron can also potentiate cell death via the lipid oxidation process known as “ferroptosis”218”
From Pancreatic cancer: Advances and challenges (2023) · cites this paper as [218]
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Self-citationGSVA: gene set variation analysis for microarray and RNA-Seq data
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Self-citationInactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
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Shin, S., Nicolle, R., Jean, C., Samain, R., Ayadi, M., Raffenne, J., Brunel, A., Solorzano, J., Neuzillet, C., Joffre, C., et al. (2020) · doi:10.1101/2020.12.23.424227 · Cited by 3
Metadata
- Authors
- Badgley, M. A., Kremer, D. M., Maurer, H. C., DelGiorno, K. E., Lee, H.-J., Purohit, V., Sagalovskiy, I. R., Ma, A., Kapilian, J., Firl, C. E. M., Decker, A. R., Sastra, S. A., Palermo, C. F., Andrade, L. R., Sajjakulnukit, P., Zhang, L., Tolstyka, Z. P., Hirschhorn, T., Lamb, C., Liu, T., Gu, W., Seeley, E. S., Stone, E., Georgiou, G., Manor, U., Iuga, A., Wahl, G. M., Stockwell, B. R., Lyssiotis, C. A., & Olive, K. P.
- Affiliations
- Columbia University Irving Medical Center (US)
- University of Michigan (US)
- Salk Institute for Biological Studies (US)
- Division of Digestive and Liver Diseases, Department of Medicine, Columbia University Medical Center, New York, NY 10032, USA.
- Columbia University (US)
- The University of Texas at Austin (US)
- University of California, San Francisco (US)
- Corresponding author
- Kremer, Daniel M.
- Maurer, H. Carlo
- Olive, Kenneth P.
- ORCID
- Badgley, Michael A.
- Kremer, Daniel M.
- Maurer, H. Carlo
- DelGiorno, Kathleen E.
- Lee, Ho-Joon
- Purohit, Vinee
- Sagalovskiy, Irina R.
- Ma, Alice
- Kapilian, Jonathan
- Decker, Amanda R.
- Palermo, Carmine F.
- Andrade, Leonardo R.
- Sajjakulnukit, Peter
- Zhang, Li
- Hirschhorn, Tal
- Lamb, Candice
- Liu, Tong
- Gu, Wei
- Stone, Everett
- Georgiou, George
- Manor, Uri
- Iuga, Alina
- Wahl, Geoffrey M.
- Stockwell, Brent R.
- Lyssiotis, Costas A.
- Olive, Kenneth P.
- Venue
- Science
- Published
- 2020-04-03
- Volume
- 368
- Issue
- 6486
- Pages
- 85-89
- ISSN
- 0036-8075 (ISSN-L)
- 1095-9203
- PMC
- PMC7681911
- OpenAlex
- W3015020891
- Cited by
- 1,294
- References
- 41
- Citations by year
- 2026: 165 · 2025: 206 · 2024: 253 · 2023: 230 · 2022: 210 · 2021: 171 · 2020: 58
- FWCI
- 94.16
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Science (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institutes of Health (T32 A009503, F31 CA180738, 1R01CA215607, P30CA013696, U24-DK097153, P01CA087497, CA189623, CA014195, R35 CA197687, Cancer Center Core Grant CA014195, CA197687)
- National Cancer Institute (CA224272, R35CA209896)
- Damon Runyon Cancer Research Foundation (DFS-09-14)
- U.S. Department of Education
- U.S. Department of Defense (W81XWH-17-1-0497)
- Lustgarten Foundation (2011 Innovator Award)
- Sidney Kimmel Foundation for Cancer Research (SKF-16-005)
- Pancreatic Cancer Action Network (13-70-25-LYSS)
- The V Foundation for Cancer Research (V2016-009)
- Waitt Foundation
- Salk Women and Special Science Award
- The Freeberg Foundation (N/A)
- Leona M. and Harry B. Helmsley Charitable Trust (2012-PG-MED002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Ferroptosis and cancer prognosis
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Keywords
- ferroptosis, cysteine depletion, pancreatic cancer, lipid reactive oxygen species, cancer therapy, tumor growth inhibition
- MeSH terms
- Ferroptosis, Animals, Cystathionine gamma-Lyase, Cysteine, Cystine, Humans, Mice, Mutant Strains, Pancreatic Neoplasms, Gene Deletion, Carcinoma, Pancreatic Ductal, Cationic Amino Acid Transporter 1, Cell Line, Tumor, Mice
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