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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Depletion of CoA contributes to the induction of ferroptosis by erastin.
“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]
The passage discussing Fig. 3E–F reports that system xC– inhibition reduced CoA levels and that added CoA prevented ferroptosis induced by imidazole ketone erastin (IKE) in human PDAC cells. This supports a contribution from CoA depletion, but the experiments used IKE rather than erastin itself. (LLM, conf=0.83)
Experimental — accuracy not yet measuredLabile iron can potentiate cell death via ferroptosis.
“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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Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2
Love, M. I., Huber, W., & Anders, S. (2014) · Genome Biology · doi:10.1186/s13059-014-0550-8 · Cited by 95,106 · see citing works
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
limma powers differential expression analyses for RNA-sequencing and microarray studies
Ritchie, M. E., Phipson, B., Wu, D., Hu, Y., Law, C. W., Shi, W., & Smyth, G. K. (2015) · Nucleic Acids Research · doi:10.1093/nar/gkv007 · Cited by 40,458 · see citing works
Conducting Meta-Analyses in <i>R</i> with the <b>metafor</b> Package
Viechtbauer, W. (2010) · Journal of Statistical Software · doi:10.18637/jss.v036.i03 · Cited by 20,464 · see citing works
Ferroptosis: An Iron-Dependent Form of Nonapoptotic Cell Death
Dixon, S. J., Lemberg, K. M., Lamprecht, M. R., Skouta, R., Zaitsev, E. M., Gleason, C. E., Patel, D. N., Bauer, A. J., Cantley, A. M., Yang, W. S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.042 · Cited by 18,691 · see citing works
Self-citationGSVA: gene set variation analysis for microarray and RNA-Seq data
Hänzelmann, S., Castelo, R., & Guinney, J. (2013) · BMC Bioinformatics · doi:10.1186/1471-2105-14-7 · Cited by 15,440 · see citing works
Regulation of Ferroptotic Cancer Cell Death by GPX4
Yang, W. S., SriRamaratnam, R., Welsch, M. E., Shimada, K., Skouta, R., Viswanathan, V. S., Cheah, J. H., Clemons, P. A., Shamji, A. F., Clish, C. B., et al. (2014) · Cell · doi:10.1016/j.cell.2013.12.010 · Cited by 7,713 · see citing works
Self-citationInactivation of the ferroptosis regulator Gpx4 triggers acute renal failure in mice
Friedmann Angeli, J. P., Schneider, M., Proneth, B., Tyurina, Y. Y., Tyurin, V. A., Hammond, V. J., Herbach, N., Aichler, M., Walch, A., Eggenhofer, E., et al. (2014) · Nature Cell Biology · doi:10.1038/ncb3064 · Cited by 3,732 · see citing works
Self-citationGenomic analyses identify molecular subtypes of pancreatic cancer
Bailey, P., Chang, D. K., Nones, K., Johns, A. L., Patch, A.-M., Gingras, M.-C., Miller, D. K., Christ, A. N., Bruxner, T. J. C., Quinn, M. C., et al. (2016) · Nature · doi:10.1038/nature16965 · Cited by 3,621 · see citing works
GEOquery: a bridge between the Gene Expression Omnibus (GEO) and BioConductor
Davis, S. R., & Meltzer, P. S. (2007) · Bioinformatics · doi:10.1093/bioinformatics/btm254 · Cited by 3,287 · see citing works
Olive, K. P., Jacobetz, M. A., Davidson, C. J., Gopinathan, A., McIntyre, D., Honess, D., Madhu, B., Goldgraben, M. A., Caldwell, M. E., Allard, D., et al. (2009) · Science · doi:10.1126/science.1171362 · Cited by 3,170 · see citing works
Self-citationHingorani, S. R., Wang, L., Multani, A. S., Combs, C., Deramaudt, T. B., Hruban, R. H., Rustgi, A. K., Chang, S., & Tuveson, D. A. (2005) · Cancer Cell · doi:10.1016/j.ccr.2005.04.023 · Cited by 2,609 · see citing works
Preinvasive and invasive ductal pancreatic cancer and its early detection in the mouse
Hingorani, S. R., Petricoin, E. F., Maitra, A., Rajapakse, V., King, C., Jacobetz, M. A., Ross, S., Conrads, T. P., Veenstra, T. D., Hitt, B. A., et al. (2003) · Cancer Cell · doi:10.1016/s1535-6108(03)00309-x · Cited by 2,471 · see citing works
Oncogene-induced Nrf2 transcription promotes ROS detoxification and tumorigenesis
DeNicola, G. M., Karreth, F. A., Humpton, T. J., Gopinathan, A., Wei, C., Frese, K., Mangal, D., Yu, K. H., Yeo, C. J., Calhoun, E. S., et al. (2011) · Nature · doi:10.1038/nature10189 · Cited by 2,277 · see citing works
Moffitt, R. A., Marayati, R., Flate, E. L., Volmar, K. E., Loeza, S. G. H., Hoadley, K. A., Rashid, N. U., Williams, L. A., Eaton, S. C., Chung, A. H., et al. (2015) · Nature Genetics · doi:10.1038/ng.3398 · Cited by 2,194 · see citing works
EMT and Dissemination Precede Pancreatic Tumor Formation
Rhim, A. D., Mirek, E. T., Aiello, N. M., Maitra, A., Bailey, J. M., McAllister, F., Reichert, M., Beatty, G. L., Rustgi, A. K., Vonderheide, R. H., et al. (2012) · Cell · doi:10.1016/j.cell.2011.11.025 · Cited by 2,136 · see citing works
Role of Mitochondria in Ferroptosis
Gao, M., Yi, J., Zhu, J., Minikes, A. M., Monian, P., Thompson, C. B., & Jiang, X. (2019) · Molecular Cell · doi:10.1016/j.molcel.2018.10.042 · Cited by 2,120 · see citing works
Dixon, S. J., Patel, D. N., Welsch, M., Skouta, R., Lee, E. D., Hayano, M., Thomas, A. G., Gleason, C. E., Tatonetti, N. P., Slusher, B. S., et al. (2014) · eLife · doi:10.7554/elife.02523 · Cited by 2,088 · see citing works
Self-citationFerroptosis is an autophagic cell death process
Gao, M., Monian, P., Pan, Q., Zhang, W., Xiang, J., & Jiang, X. (2016) · Cell Research · doi:10.1038/cr.2016.95 · Cited by 1,899 · see citing works
A Model-Based Background Adjustment for Oligonucleotide Expression Arrays
Wu, Z. J., Irizarry, R. A., Gentleman, R. C., Martínez-Murillo, F., & Spencer, F. A. (2004) · Journal of the American Statistical Association · doi:10.1198/016214504000000683 · Cited by 1,717 · see citing works
Global survey of cell death mechanisms reveals metabolic regulation of ferroptosis
Shimada, K., Skouta, R., Kaplan, A., Yang, W. S., Hayano, M., Dixon, S. J., Brown, L. M., Valenzuela, C. A., Wolpaw, A. J., & Stockwell, B. R. (2016) · Nature Chemical Biology · doi:10.1038/nchembio.2079 · Cited by 1,017 · see citing works
Self-citationImidazole Ketone Erastin Induces Ferroptosis and Slows Tumor Growth in a Mouse Lymphoma Model
Zhang, Y., Tan, H., Daniels, J. D., Zandkarimi, F., Liu, H., Brown, L. M., Uchida, K., O’Connor, O. A., & Stockwell, B. R. (2019) · Cell chemical biology · doi:10.1016/j.chembiol.2019.01.008 · Cited by 729 · see citing works
Self-citationFKBP51 Affects Cancer Cell Response to Chemotherapy by Negatively Regulating Akt
Pei, H., Li, L., Fridley, B. L., Jenkins, G. D., Kalari, K. R., Lingle, W., Petersen, G., Lou, Z., & Wang, L. (2009) · Cancer Cell · doi:10.1016/j.ccr.2009.07.016 · Cited by 709 · see citing works
Cramer, S. L., Saha, A., Liu, J., Tadi, S., Tiziani, S., Yan, W., Triplett, K., Lamb, C., Alters, S. E., Rowlinson, S. W., et al. (2016) · Nature Medicine · doi:10.1038/nm.4232 · Cited by 541 · see citing works
Self-citationRedox imbalance in cystine/glutamate transporter-deficient mice
Sato, H., Shiiya, A., Kimata, M., Maebara, K., Tamba, M., Sakakura, Y., Makino, N., Sugiyama, F., Yagami, K.-I., Moriguchi, T., et al. (2005) · Journal of Biological Chemistry · doi:10.1074/jbc.m506439200 · Cited by 422 · see citing works
A Novel MIF Signaling Pathway Drives the Malignant Character of Pancreatic Cancer by Targeting NR3C2
Yang, S., He, P., Wang, J., Schetter, A. J., Tang, W., Funamizu, N., Yanaga, K. K., Uwagawa, T., Satoskar, A. R., Gaedcke, J., et al. (2016) · Cancer Research · doi:10.1158/0008-5472.can-15-2841 · Cited by 393 · see citing works
High-Efficiency FLP and ΦC31 Site-Specific Recombination in Mammalian Cells
Raymond, C. S., & Soriano, P. M. (2007) · PLoS ONE · doi:10.1371/journal.pone.0000162 · Cited by 385 · see citing works
Carrière, C., Young, A. L., Gunn, J. R., Longnecker, D. S., & Korc, M. (2009) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2009.03.068 · Cited by 236 · see citing works
Integrative Survival-Based Molecular Profiling of Human Pancreatic Cancer
Donahue, T. R., Tran, L. M., Hill, R., Li, Y., Kovochich, A., Calvopina, J. H., Patel, S. G., Wu, N., Hindoyan, A. A., Farrell, J. J., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-1539 · Cited by 212 · see citing works
Daher, B., Parks, S. K., Durivault, J., Cormerais, Y., Baidarjad, H., Tambutté, É., Pouysségur, J., & Vučetić, M. (2019) · Cancer Research · doi:10.1158/0008-5472.can-18-3855 · Cited by 203 · see citing works
Grützmann, R., Pilarsky, C. P., Ammerpohl, O., Lüttges, J., Böhme, A., Sipos, B., Foerder, M., Alldinger, I., Jahnke, B., Schackert, H. K., et al. (2004) · Neoplasia · doi:10.1593/neo.04295 · Cited by 198 · see citing works
Hiraoka, N., Yamazaki–Itoh, R., Ino, Y., Mizuguchi, Y., Yamada, T., Hirohashi, S., & Kanai, Y. (2010) · Gastroenterology · doi:10.1053/j.gastro.2010.10.009 · Cited by 175 · see citing works
Deubiquitinases Maintain Protein Homeostasis and Survival of Cancer Cells upon Glutathione Depletion
Harris, I. S., Endress, J. E., Coloff, J. L., Selfors, L. M., McBrayer, S. K., Rosenbluth, J. M., Takahashi, N., Dhakal, S., Koduri, V., Oser, M. G., et al. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.01.020 · Cited by 168 · see citing works
RTCGAToolbox: A New Tool for Exporting TCGA Firehose Data
Samur, M. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106397 · Cited by 160 · see citing works
Extracellular 4′-phosphopantetheine is a source for intracellular coenzyme A synthesis
Srinivasan, B., Baratashvili, M., van der Zwaag, M., Kanon, B., Colombelli, C., Lambrechts, R. A., Schaap, O., Nollen, E. A. A., Podgoršek, A., Kosec, G., et al. (2015) · Nature Chemical Biology · doi:10.1038/nchembio.1906 · Cited by 127 · see citing works
Leu, J. I.-J., Murphy, M. E., & George, D. L. (2019) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1821277116 · Cited by 112 · see citing works
Carrière, C., Young, A. L., Gunn, J. R., Longnecker, D. S., & Korc, M. (2011) · PLoS ONE · doi:10.1371/journal.pone.0027725 · Cited by 77 · see citing works
Rückert, F., Hennig, M. J. P., Petraki, C. D., Wehrum, D., Distler, M., Denz, A., Schroeder, M., Dawelbait, G., Kalthoff, H., Hd, S., et al. (2008) · British Journal of Cancer · doi:10.1038/sj.bjc.6604717 · Cited by 70 · see citing works
Quantification of Murine Pancreatic Tumors by High-Resolution Ultrasound
Sastra, S. A., & Olive, K. P. (2012) · Methods in molecular biology · doi:10.1007/978-1-62703-287-2_13 · Cited by 58 · see citing works
Self-citationKshattry, S., Saha, A., Gries, P., Tiziani, S., Stone, E. M., Georgiou, G., & DiGiovanni, J. (2019) · npj Precision Oncology · doi:10.1038/s41698-019-0088-z · Cited by 55 · see citing works
Self-citationEberle-Singh, J. A., Sagalovskiy, I. R., Maurer, H. C., Sastra, S. A., Palermo, C. F., Decker-Farrell, A. R., Kim, M. J., Sheedy, J., Mollin, A., Cao, L., et al. (2019) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-3281 · Cited by 35 · see citing works
Self-citation
Flagged first, then by citations
Research works printed but not linked: 4
- [36]Subramanian A, Gene set enrichment analysis: a knowledge-based approach for interpreting genome-wide expression profiles. Proc. Natl. Acad. Sci. U S A 102, 15545– 15550 (2005). 16199517 PMC1239896
- [38]Therneau TM, Grambsch PM, Modeling Survival Data: Extending the Cox Model. Statistics for Biology and Health (Springer New York, 2013).
- [41]Hingorani SR, Trp53R172H and KrasG12D cooperate to promote chromosomal instability and widely metastatic pancreatic ductal adenocarcinoma in mice. Cancer Cell 7, 469– 483 (2005). 15894267
- [46]Sastra SA, Olive KP, Quantification of murine pancreatic tumors by high-resolution ultrasound. Methods Mol. Biol 980, 249– 266 (2013). 23359158 PMC3879959
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Zheng, J., & Conrad, M. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.10.011 · Cited by 1,338 · see citing works
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Tang, R., Xu, J., Zhang, B., Liu, J., Liang, C., Hua, J., Meng, Q., Yu, X., & Shi, S. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00946-7 · Cited by 1,280 · see citing works
Niu, B., Liao, K., Zhou, Y., Wen, T., Quan, G., Pan, X., & Wu, C. (2021) · Biomaterials · doi:10.1016/j.biomaterials.2021.121110 · Cited by 1,168 · see citing works
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Newton, K., Strasser, A., Kayagaki, N., & Dixit, V. M. (2024) · Cell · doi:10.1016/j.cell.2023.11.044 · Cited by 1,029 · see citing works
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Liu, J., Xia, X., & Huang, P. (2020) · Molecular Therapy · doi:10.1016/j.ymthe.2020.08.021 · Cited by 348 · see citing works
Cell death in pancreatic cancer: from pathogenesis to therapy
Chen, X., Zeh, H. J., Kang, R., Kroemer, G., & Tang, D. (2021) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-021-00486-6 · Cited by 338 · see citing works
Bayır, H., Dixon, S. J., Tyurina, Y. Y., Kellum, J. A., & Kagan, V. E. (2023) · Nature Reviews Nephrology · doi:10.1038/s41581-023-00689-x · Cited by 346 · see citing works
The therapeutic potential of targeting regulated non-apoptotic cell death
Hadian, K., & Stockwell, B. R. (2023) · Nature Reviews Drug Discovery · doi:10.1038/s41573-023-00749-8 · Cited by 335 · see citing works
Self-citationMetabolic orchestration of the wound healing response
Eming, S. A., Murray, P. J., & Pearce, E. J. (2021) · Cell Metabolism · doi:10.1016/j.cmet.2021.07.017 · Cited by 319 · see citing works
Emerging mechanisms and targeted therapy of ferroptosis in cancer
Wang, H., Cheng, Y., Mao, C., Liu, S., Xiao, D., Huang, J. X., & Tao, Y. (2021) · Molecular Therapy · doi:10.1016/j.ymthe.2021.03.022 · Cited by 320 · see citing works
Disulfidptosis: disulfide stress–induced cell death
Liu, X., Zhuang, L., & Gan, B. (2023) · Trends in Cell Biology · doi:10.1016/j.tcb.2023.07.009 · Cited by 317 · see citing works
Baicalin induces ferroptosis in bladder cancer cells by downregulating FTH1
Kong, N., Chen, X., Feng, J., Duan, T., Liu, S., Sun, X., Chen, P., Pan, T. S., Yan, L., Jin, T., et al. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2021.03.036 · Cited by 303 · see citing works
The Role of NCOA4-Mediated Ferritinophagy in Ferroptosis
Santana-Codina, N., Gikandi, A., & Mancias, J. D. (2021) · Advances in experimental medicine and biology · doi:10.1007/978-3-030-62026-4_4 · Cited by 315 · see citing works
Amino Acids and Their Transporters in T Cell Immunity and Cancer Therapy
Wang, W., & Zou, W. (2020) · Molecular Cell · doi:10.1016/j.molcel.2020.09.006 · Cited by 304 · see citing works
Ferroptosis: principles and significance in health and disease
Chen, F., Kang, R., Tang, D., & Liu, J. (2024) · Journal of Hematology & Oncology · doi:10.1186/s13045-024-01564-3 · Cited by 313 · see citing works
A guideline on the molecular ecosystem regulating ferroptosis
Dai, E., Chen, X., Linkermann, A., Jiang, X., Kang, R., Kagan, V. E., Bayır, H., Yang, W. S., García‐Sáez, A. J., Ioannou, M. S., et al. (2024) · Nature Cell Biology · doi:10.1038/s41556-024-01360-8 · Cited by 308 · see citing works
Self-citationSignaling pathways in cancer metabolism: mechanisms and therapeutic targets
You, M., Xie, Z., Zhang, N., Zhang, Y., Xiao, D., Liu, S., Zhuang, W., Li, L., & Tao, Y. (2023) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-023-01442-3 · Cited by 297 · see citing works
Lu, Y., Zhao, M., Luo, Q.-W., Zhang, Y., Liu, T.-T., Yang, Z., Liao, M., Tu, P., & Zeng, K. (2022) · ACS Nano · doi:10.1021/acsnano.2c01619 · Cited by 293 · see citing works
Self-citationOxidative Stress in the Tumor Microenvironment and Its Relevance to Cancer Immunotherapy
Aboelella, N. S., Brandle, C., Kim, T., Ding, Z., & Zhou, G. (2021) · Cancers · doi:10.3390/cancers13050986 · Cited by 295 · see citing works
Emerging Roles of Energy Metabolism in Ferroptosis Regulation of Tumor Cells
Yao, X., Li, W., Fang, D., Xiao, C., Wu, X. W., Li, M., & Luo, Z. Y. (2021) · Advanced Science · doi:10.1002/advs.202100997 · Cited by 281 · see citing works
The Role of Cystine/Glutamate Antiporter SLC7A11/xCT in the Pathophysiology of Cancer
Jyotsana, N., Ta, K. T. L., & DelGiorno, K. E. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.858462 · Cited by 275 · see citing works
Self-citationZhang, Z., Zeng, X., Wu, Y., Liu, Y., Zhang, X., & Song, Z. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.925618 · Cited by 275 · see citing works
Feng, L., Zhao, K., Sun, L., Yin, X., Zhang, J., Liu, C., & Li, B. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-03042-7 · Cited by 277 · see citing works
Activation of lysosomal iron triggers ferroptosis in cancer
Cañeque, T., Baron, L., Müller, S., Carmona, A., Colombeau, L., Versini, A., Solier, S., Gaillet, C., Sindikubwabo, F., Sampaio, J. L., et al. (2025) · Nature · doi:10.1038/s41586-025-08974-4 · Cited by 287 · see citing works
Self-citationGPX4-independent ferroptosis—a new strategy in disease’s therapy
Ma, T., Du, J., Zhang, Y., Wang, Y., Wang, B., & Zhang, T. (2022) · Cell Death Discovery · doi:10.1038/s41420-022-01212-0 · Cited by 275 · see citing works
FBW7-NRA41-SCD1 axis synchronously regulates apoptosis and ferroptosis in pancreatic cancer cells
Zeng, Y., Zhuo, Q., Hu, Q., Xu, X., Liu, M., Zhang, Z., Xu, W., Liu, W., Fan, G., Qin, Y., et al. (2020) · Redox Biology · doi:10.1016/j.redox.2020.101807 · Cited by 271 · see citing works
Amino Acid Depletion Therapies: Starving Cancer Cells to Death
Butler, M., van der Meer, L. T., & van Leeuwen, F. N. (2021) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2021.03.003 · Cited by 270 · see citing works
Persister cancer cells: Iron addiction and vulnerability to ferroptosis
Rodriguez, R., Schreiber, S. L., & Conrad, M. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.12.001 · Cited by 271 · see citing works
Molecular mechanisms of ferroptosis and relevance to inflammation
Deng, L., He, S., Guo, N., Tian, W., Zhang, W., & Luo, L. (2022) · Inflammation Research · doi:10.1007/s00011-022-01672-1 · Cited by 269 · see citing works
Stem Cell Factor SOX2 Confers Ferroptosis Resistance in Lung Cancer via Upregulation of SLC7A11
Wang, X., Chen, Y., Wang, X., Tian, H., Wang, Y., Jin, J., Shan, Z., Liu, Y., Cai, Z., Tong, X., et al. (2021) · Cancer Research · doi:10.1158/0008-5472.can-21-0567 · Cited by 265 · see citing works
Song, X., Liu, J., Kuang, F., Chen, X., Zeh, H. J., Kang, R., Kroemer, G., Xie, Y., & Tang, D. (2021) · Cell Reports · doi:10.1016/j.celrep.2021.108767 · Cited by 258 · see citing works
Functional states of myeloid cells in cancer
van Vlerken-Ysla, L. E., Tyurina, Y. Y., Kagan, V. E., & Gabrilovich, D. I. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.009 · Cited by 263 · see citing works
Ferroptosis: when metabolism meets cell death
Zheng, J., & Conrad, M. (2024) · Physiological Reviews · doi:10.1152/physrev.00031.2024 · Cited by 270 · see citing works
GOT1 inhibition promotes pancreatic cancer cell death by ferroptosis
Kremer, D. M., Nelson, B. S., Lin, L., Yarosz, E. L., Halbrook, C. J., Kerk, S. A., Sajjakulnukit, P., Myers, A. L., Thurston, G., Hou, S. W., et al. (2021) · Nature Communications · doi:10.1038/s41467-021-24859-2 · Cited by 262 · see citing works
Self-citationWu, C., Liu, Z., Chen, Z., Xu, D., Chen, L., Lin, H., & Shi, J. (2021) · Science Advances · doi:10.1126/sciadv.abj8833 · Cited by 254 · see citing works
Wang, Y., Cheng, H., Wang, T., Zhang, K., Zhang, Y., & Kang, X. (2023) · Cell Proliferation · doi:10.1111/cpr.13448 · Cited by 239 · see citing works
Zhang, Q., Deng, T., Zhang, H., Zuo, D., Zhu, Q., Bai, M., Liu, R., Ning, T., Zhang, L., Yu, Z., et al. (2022) · Advanced Science · doi:10.1002/advs.202203357 · Cited by 230 · see citing works
Self-citationHIF-2α activation potentiates oxidative cell death in colorectal cancers by increasing cellular iron
Singhal, R., Mitta, S. R., Das, N. K., Kerk, S. A., Sajjakulnukit, P., Solanki, S., Andren, A., Kumar, R., Olive, K. P., Banerjee, R., et al. (2021) · Journal of Clinical Investigation · doi:10.1172/jci143691 · Cited by 215 · see citing works
Self-citationCathepsin B in programmed cell death machinery: mechanisms of execution and regulatory pathways
Xie, Z., Zhao, M., Yan, C., Kong, W., Lan, F., Narengaowa, Zhao, S., Yang, Q., Bai, Z., Qing, H., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05786-0 · Cited by 217 · see citing works
Metabolic cell death in cancer: ferroptosis, cuproptosis, disulfidptosis, and beyond
Mao, C., Wang, M., Zhuang, L., & Gan, B. (2024) · Protein & Cell · doi:10.1093/procel/pwae003 · Cited by 224 · see citing works
Ferroptosis: A flexible constellation of related biochemical mechanisms
Dixon, S. J., & Pratt, D. A. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.03.005 · Cited by 211 · see citing works
ENO1 suppresses cancer cell ferroptosis by degrading the mRNA of iron regulatory protein 1
Zhang, T., Sun, L., Hao, Y., Suo, C., Shen, S., Wei, H., Ma, W., Zhang, P., Wang, T., Gu, X., et al. (2021) · Nature Cancer · doi:10.1038/s43018-021-00299-1 · Cited by 206 · see citing works
Effects of dietary intervention on human diseases: molecular mechanisms and therapeutic potential
Xiao, Y.-L., Gong, Y., Qi, Y.-J., Shao, Z., & Jiang, Y.-Z. (2024) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-024-01771-x · Cited by 212 · see citing works
Yang, W., Wang, Y., Zhang, C., Huang, Y., Yu, J., Shi, L., Zhang, P., Yin, Y., Li, R., & Tao, K. (2022) · Frontiers in Pharmacology · doi:10.3389/fphar.2022.865689 · Cited by 205 · see citing works
SLC7A11 as a Gateway of Metabolic Perturbation and Ferroptosis Vulnerability in Cancer
Lee, J., & Roh, J. (2022) · Antioxidants · doi:10.3390/antiox11122444 · Cited by 206 · see citing works
Ferroptosis as a potential target for cancer therapy
Chen, Z., Wang, W., Razak, S. R. A., Han, T., Ahmad, N. H., & Li, X. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-05930-w · Cited by 208 · see citing works
MGST1 is a redox-sensitive repressor of ferroptosis in pancreatic cancer cells
Kuang, F., Liu, J., Xie, Y., Tang, D., & Kang, R. (2021) · Cell Chemical Biology · doi:10.1016/j.chembiol.2021.01.006 · Cited by 199 · see citing works
The pleiotropic functions of reactive oxygen species in cancer
Wu, K., Zowalaty, A. E. E., Sayin, V. I., & Papagiannakopoulos, T. Y. (2024) · Nature Cancer · doi:10.1038/s43018-024-00738-9 · Cited by 203 · see citing works
Du, J., Wang, X., Li, Y., Ren, X., Zhou, Y., Hu, W., Zhou, C., Jing, Q., Yang, C., Wang, L., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03996-y · Cited by 197 · see citing works
Role of mitochondrial alterations in human cancer progression and cancer immunity
Wang, S., Tseng, L., & Lee, H. (2023) · Journal of Biomedical Science · doi:10.1186/s12929-023-00956-w · Cited by 208 · see citing works
Self-citationZheng, X. W., Wang, Q., Zhou, Y., Zhang, D., Geng, Y., Hu, W., Wu, C., Shi, Y., & Jiang, J. (2022) · 癌症：英文版 · doi:10.1002/cac2.12363 · Cited by 196 · see citing works
Pharmacologic Screening Identifies Metabolic Vulnerabilities of CD8+ T Cells
Drijvers, J. M., Gillis, J. E., Muijlwijk, T., Nguyen, T. H., Gaudiano, E. F., Harris, I. S., LaFleur, M. W., Ringel, A. E., Yao, C.-H., Kurmi, K., et al. (2020) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-20-0384 · Cited by 190 · see citing works
Upadhyayula, P. S., Higgins, D. M. O., Mela, A., Banu, M. A., Dovas, A., Zandkarimi, F., Patel, P. R., Mahajan, A., Humala, N., Nguyen, T. T. T., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36630-w · Cited by 191 · see citing works
Self-citationCDKN2A deletion remodels lipid metabolism to prime glioblastoma for ferroptosis
Minami, J. K., Morrow, D., Bayley, N. A., Fernandez, E. G., Salinas, J. J., Tse, C., Zhu, H., Su, B., Plawat, R., Jones, A. E., et al. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.05.001 · Cited by 196 · see citing works
Sun, J., Zhou, C., Zhao, Y., Zhang, X.-F., Chen, W., Zhou, Q., Hu, B., Gao, D., Raatz, L., Wang, Z., et al. (2021) · Redox Biology · doi:10.1016/j.redox.2021.101942 · Cited by 190 · see citing works
STAT6 inhibits ferroptosis and alleviates acute lung injury via regulating P53/SLC7A11 pathway
Yang, Y., Ma, Y., Li, Q., Ling, Y., Zhou, Y., Chu, K., Xue, L., & Tao, S. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-04971-x · Cited by 191 · see citing works
Nicolini, A., & Ferrari, P. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1353787 · Cited by 187 · see citing works
Liu, X., Zhang, Y., Zhuang, L., Olszewski, K. L., & Gan, B. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.11.010 · Cited by 184 · see citing works
Dietary regulation in health and disease
Wu, Q., Gao, Z., Yu, X., & Wang, P. (2022) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-022-01104-w · Cited by 182 · see citing works
Recommendations for robust and reproducible research on ferroptosis
Mishima, E., Nakamura, T., Doll, S. G., Proneth, B., Fedorova, M., Pratt, D. A., Angeli, J. P. F., Dixon, S. J., Wahida, A., & Conrad, M. (2025) · Nature Reviews Molecular Cell Biology · doi:10.1038/s41580-025-00843-2 · Cited by 191 · see citing works
Lei, H.-L., Pei, Z.-F., Jiang, C., & Cheng, L. (2023) · Exploration · doi:10.1002/exp.20220001 · Cited by 105 · see citing works
Cassim, S., Vučetić, M., Ždralević, M., & Pouysségur, J. (2020) · Cancers · doi:10.3390/cancers12051119 · Cited by 176 · see citing works
- 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
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › 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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