The DOI matches its Crossref record; 59 of the 60 references it cites were found in a registry or an index.
NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer
Open accessAbstract
Pancreatic cancer is a deadly malignancy that lacks effective therapeutics. We previously reported that oncogenic Kras induced the redox master regulator Nfe2l2/Nrf2 to stimulate pancreatic and lung cancer initiation. Here, we show that NRF2 is necessary to maintain pancreatic cancer proliferation by regulating mRNA translation. Specifically, loss of NRF2 led to defects in autocrine epidermal growth factor receptor (EGFR) signaling and oxidation of specific translational regulatory proteins, resulting in impaired cap-dependent and cap-independent mRNA translation in pancreatic cancer cells. Combined targeting of the EGFR effector AKT and the glutathione antioxidant pathway mimicked Nrf2 ablation to potently inhibit pancreatic cancer ex vivo and in vivo, representing a promising synthetic lethal strategy for treating the disease.
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“For example, NRF2 steers glucose to anabolic cancer metabolism and prevents oxidation of multiple translational factors to augment protein output [15,16].”
From NRF2 Activation Confers Resistance to eIF4A Inhibitors in Cancer Therapy (2021) · cites this paper as [15]
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“Indeed, NRF2 is known to augment global protein production by reducing key translation factors such as eEF2 [15].”
From NRF2 Activation Confers Resistance to eIF4A Inhibitors in Cancer Therapy (2021) · cites this paper as [15]
In the citing paper
“For example, the transcription factor Nrf2, which mediates an antioxidant response program to detoxify ROS, is downstream of several oncogenic drivers, and loss of Nrf2 in this context can impair tumor proliferation (Chio et al., 2016; DeNicola et al., 2011).”
From Targeting Metabolism for Cancer Therapy (2017) · cites this paper as Chio et al., 2016
In the citing paper
“In addition to activating the GOT2/GOT1/Malic Enzyme 1 (ME1) pathway, oncogenic KRAS activates the NRF2 antioxidant system by inducing NRF2 expression59,60 and by constitutively activating the battery of genes controlled by NRF2 to maintain the redox balance and promote tumorigenesis61.”
From The metabolic landscape of RAS-driven cancers from biology to therapy (2021) · cites this paper as [61]
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Citations
Cites
Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources
Huang, D. W., Sherman, B. T., & Lempicki, R. A. (2009) · Nature Protocols · doi:10.1038/nprot.2008.211 · Cited by 35,890 · cited 3×
“To determine whether the subset of proteins specifically oxidized in KPn cells represented any particular biochemical processes, the data were analyzed using DAVID (Huang et al., 2009) for pathway enrichment.”
InfluentialSiegel, R. L., Miller, K. D., & Jemal, A. (2015) · CA A Cancer Journal for Clinicians · doi:10.3322/caac.21254 · Cited by 11,854 · cited 2×
“This is reflected by a short median survival of 6 months and a 5-year survival of 5% (Siegel et al., 2015).”
Jemal, A., Siegel, R., Ward, E., Hao, Y., Xu, J., & Thun, M. J. (2009) · CA: A Cancer Journal for Clinicians · doi:10.3322/caac.20006 · Cited by 9,709
Ross, P. L., Huang, Y. N., Marchese, J. N., Williamson, B., Parker, K., Hattan, S., Khainovski, N., Pillai, S., Dey, S., Daniels, S., et al. (2004) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m400129-mcp200 · Cited by 4,401 · cited 1×
“This was combined with a parallel analysis of the total proteome by using amine-reactive isobaric tags for relative and absolute quantification (iTRAQ; Ross et al., 2004) (Figure 2A).”
Self-citationCore Signaling Pathways in Human Pancreatic Cancers Revealed by Global Genomic Analyses
Jones, S., Zhang, X., Parsons, D. W., Lin, J. C.-H., Leary, R. J., Angenendt, P., Mankoo, P., Carter, H., Kamiyama, H., Jimeno, A., et al. (2008) · Science · doi:10.1126/science.1164368 · Cited by 3,969 · cited 2×
“%) of activating KRASmutations and inactivation of the tumor suppressors TP53, P16/INK4A, and SMAD4 (Jones et al., 2008).”
Regulation of Translation Initiation in Eukaryotes: Mechanisms and Biological Targets
Sonenberg, N., & Hinnebusch, A. G. (2009) · Cell · doi:10.1016/j.cell.2009.01.042 · Cited by 3,304 · cited 2×
“…cysteinemodifications, prompting us to further evaluate the functional role of Nrf2 inmRNA translation for pancreatic cancer cells. mRNA Translation Is Impeded in Nrf2-Deficient Cells mRNA translation is a vital cellular process that regulates growth and metabolism (Sonenberg and Hinnebusch, 2009).”
Self-citationMaehama, T., & Dixon, J. E. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.22.13375 · Cited by 3,104
Hingorani, 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
Self-citationOncogene-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 · cited 2×
“We previously found that oncogenic Kras expression induced an important regulator of redox control, the transcription factor nuclear factor erythroid-derived 2-like 2, Nfe2l2/Nrf2 (DeNicola et al., 2011).”
Self-citationThe Nrf2 regulatory network provides an interface between redox and intermediary metabolism
Hayes, J. D., & Dinkova‐Kostova, A. T. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.02.002 · Cited by 2,210
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Reactive Oxygen Species, Toxicity, Oxidative Stress, and Antioxidants: Chronic Diseases and Aging
Jomova, K., Raptova, R., Alomar, S. Y., Alwasel, S. H., Nepovimova, E., Kuca, K., & Valko, M. (2023) · Archives of Toxicology · doi:10.1007/s00204-023-03562-9 · Cited by 2,638
Transcriptional Regulation by Nrf2
Tonelli, C., Chio, I. I. C., & Tuveson, D. A. (2017) · Antioxidants and Redox Signaling · doi:10.1089/ars.2017.7342 · Cited by 2,280
Self-citationRAS Proteins and Their Regulators in Human Disease
Simanshu, D. K., Nissley, D. V., & McCormick, F. (2017) · Cell · doi:10.1016/j.cell.2017.06.009 · Cited by 1,943
The KEAP1-NRF2 system: a thiol-based sensor-effector apparatus for maintaining redox homeostasis
Yamamoto, M., Kensler, T. W., & Motohashi, H. (2018) · Physiological Reviews · doi:10.1152/physrev.00023.2017 · Cited by 1,968
NRF2 and the Hallmarks of Cancer
Rojo de la Vega, M., Chapman, E., & Zhang, D. D. (2018) · Cancer Cell · doi:10.1016/j.ccell.2018.03.022 · Cited by 1,672
Metadata
- Authors
- Chio, I. I. C., Jafarnejad, S. M., Ponz-Sarvise, M., Park, Y., Rivera, K., Palm, W., Wilson, J., Sangar, V., Hao, Y., Öhlund, D., Wright, K., Filippini, D., Lee, E. J., Da Silva, B., Schoepfer, C., Wilkinson, J. E., Buscaglia, J. M., DeNicola, G. M., Tiriac, H., Hammell, M., Crawford, H. C., Schmidt, E. E., Thompson, C. B., Pappin, D. J., Sonenberg, N., & Tuveson, D. A.
- Affiliations
- Cold Spring Harbor Laboratory (US)
- McGill University (CA)
- Memorial Sloan Kettering Cancer Center (US)
- Institute for Systems Biology (US)
- University of Michigan (US)
- Stony Brook School (US)
- Cornell University (US)
- Montana State University (US)
- Corresponding author
- Tuveson, David A.
- ORCID
- Chio, Iok In Christine
- Jafarnejad, Seyed Mehdi
- Park, Youngkyu
- Rivera, Keith
- Palm, Wilhelm
- Öhlund, Daniel
- Filippini, Dea
- Lee, Eun Jung
- Wilkinson, John Erby
- Buscaglia, Jonathan M.
- DeNicola, Gina M.
- Hammell, Molly
- Crawford, Howard C.
- Schmidt, Edward E.
- Thompson, Craig B.
- Pappin, Darryl J.
- Sonenberg, Nahum
- Tuveson, David A.
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-08
- Volume
- 166
- Issue
- 4
- Pages
- 963-976
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC5234705
- OpenAlex
- W2495582206
- Cited by
- 378
- References
- 60
- Citations by year
- 2026: 14 · 2025: 16 · 2024: 31 · 2023: 54 · 2022: 35 · 2021: 54 · 2020: 42 · 2019: 40 · 2018: 43 · 2017: 40 · 2016: 9
- FWCI
- 22.86
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (submittedVersion)
- eScholarship@McGill (McGill) (submittedVersion, cc-by-nc-nd)
- Funders
- Cancer Center Support (5P30CA045508, P30CA008748)
- CSHL Association
- NIH (5P30CA45508-26, 5P50CA101955-07, 1U10CA180944-01, 5U01CA168409-3, 1R01CA190092-01, AG040020, CA152559, R01 CA159222)
- Carcinoid Foundation
- PCUK
- David Rubinstein Center for Pancreatic Cancer Research at MSKCC
- Stand Up to Cancer
- KWF
- STARR Foundation (I7-A718)
- DOD (W81XWH-13-PRCRP-IA)
- Precision Medicine Research Associates
- Damon Runyon Cancer Research Foundation (DRG-2165-13)
- Human Frontier Science Program (LT000190/2013)
- Cancer Research Society and CCSRI (702317)
- Canadian Institute of Health Research
- Swedish Research Council (537-2013-7277)
- Sociedad Española de Oncología Médica
- Hope Funds for Cancer Research Fellowship
- MSKCC Molecular Cytology Core
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Redox biology and oxidative stress
- Keywords
- Nrf2, pancreatic cancer, mRNA translation, KRAS, EGFR signaling, autocrine signaling, protein oxidation, cap-dependent translation, cap-independent translation, Akt, synthetic lethality, tumor maintenance
- MeSH terms
- Animals, Cysteine, Glutathione, Humans, Organoids, Pancreatic Neoplasms, Protein Biosynthesis, Signal Transduction, Proto-Oncogene Proteins p21(ras), Autocrine Communication, NF-E2-Related Factor 2, Mice
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