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CUL3 and NRF2 Mutations Confer an NRF2 Activation Phenotype in a Sporadic Form of Papillary Renal Cell Carcinoma
Published version of a preprint
Abstract
Sustained activation of the stress-regulated transcription factor NRF2 (NFE2L2) is a prominent feature of many types of cancer, implying that mutations driving NRF2 may be important to tumor progression. In hereditary type 2 papillary renal cell carcinoma (PRCC2, also known as hereditary leiomyomatosis and renal cell cancer), NRF2 activation is a direct consequence of the accumulation of intracellular fumarate, a result of fumarate hydratase (FH) inactivation, but it is not clear how NRF2 may be activated in sporadic forms of PRCC2. Here we show that somatic mutations in NRF2, CUL3, and SIRT1 are responsible for driving the NRF2 activation phenotype in sporadic PRCC2. Transcriptome sequencing revealed the expression pattern of mutant alleles of NRF2, CUL3, and SIRT1 and also confirmed NRF2 activation in clinical specimens. Our results show a convergence in somatic mutations in sporadic PRCC2 with FH mutation in hereditary PRCC2. Cancer Res; 73(7); 2044–51. ©2013 AACR.
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“Some somatic mutations give rise to hyperactive Nrf2, which causes enhanced antioxidant capacity and confers protection of cancer cells from ROS and cancer therapy, thereby leading to cancer cell growth and proliferation, cancer progression, and cancer therapy resistance (e.g., chemoresistance) (Figure 8) [161,162,163,164,165,166,167,168,169,170,171].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [166]
In the citing paper
“most of which have been attributed to loss-of-function mutations in the KEAP1 gene and/or gain-of-function mutations in the NFE2L2 gene encoding Nrf2 [162,163,164,166,167].”
From Nrf2 and Oxidative Stress: A General Overview of Mechanisms and Implications in Human Disease (2022) · cites this paper as [166]
Citations
Cites
R: A Language and Environment for Statistical Computing
R Core Team (2000) · doi:10.32614/r.manuals · Cited by 355,893
Controlling the False Discovery Rate: A Practical and Powerful Approach to Multiple Testing
Benjamini, Y., & Hochberg, Y. (1995) · Journal of the Royal Statistical Society Series B: Statistical Methodology · doi:10.1111/j.2517-6161.1995.tb02031.x · Cited by 109,482
The Sequence Alignment/Map format and SAMtools
Li, H., Handsaker, B., Wysoker, A., Fennell, T., Ruan, J., Homer, N., Marth, G., Abecasis, G., Durbin, R., & 1000 Genome Project Data Processing Subgroup (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp352 · Cited by 62,041
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
The variant call format and VCFtools
Danecek, P., Auton, A., Abecasis, G. R., Albers, C. A., Banks, E., DePristo, M. A., Handsaker, R. E., Lunter, G. A., Marth, G., Sherry, S. T., et al. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr330 · Cited by 16,450
Differential expression analysis for sequence count data
Anders, S., & Huber, W. (2010) · Genome Biology · doi:10.1186/gb-2010-11-10-r106 · Cited by 15,581
Trapnell, C., Roberts, A., Goff, L. A., Pertea, G. M., Kim, D., Kelley, D. R., Pimentel, H., Salzberg, S. L., Rinn, J. L., & Pachter, L. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.016 · Cited by 12,145
TopHat: discovering splice junctions with RNA-Seq
Trapnell, C., Pachter, L. S., & Salzberg, S. L. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp120 · Cited by 11,682
Stress-dependent regulation of FOXO transcription factors by the SIRT1 deacetylase
Brunet, A., Sweeney, L. B., Sturgill, J. F., Chua, K. F., Greer, P. L., Lin, Y., Tran, H., Ross, S. E., Mostoslavsky, R., Cohen, H. Y., et al. (2004) · Science · doi:10.1126/science.1094637 · Cited by 3,239
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
Kobayashi, A., Kang, M.-I., Okawa, H., Ohtsuji, M., Zenke, Y., Chiba, T., Igarashi, K., & Yamamoto, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.16.7130-7139.2004 · Cited by 2,224
Dinkova-Kostova, A. T., Holtzclaw, W. D., Cole, R. N., Itoh, K., Wakabayashi, N., Katoh, Y., Yamamoto, M., & Talalay, P. (2002) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.172398899 · Cited by 1,947
The Multiple Leiomyoma Consortium (2002) · Nature Genetics · doi:10.1038/ng849 · Cited by 1,635
Dysfunctional KEAP1–NRF2 Interaction in Non-Small-Cell Lung Cancer
Singh, A., Misra, V., Thimmulappa, R. K., Lee, H., Ames, S., Hoque, M. O., Herman, J. G., Baylin, S. B., Sidransky, D., Gabrielson, E., et al. (2006) · PLoS Medicine · doi:10.1371/journal.pmed.0030420 · Cited by 1,060
Radjendirane, V., & Jaiswal, A. K. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.25.14960 · Cited by 1,034
Furukawa, M., & Xiong, Y. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.25.1.162-171.2005 · Cited by 759
Structural basis for defects of Keap1 activity provoked by its point mutations in lung cancer
Padmanabhan, B., Tong, K. I., Ohta, T., Nakamura, Y., Scharlock, M., Ohtsuji, M., Kang, M.-I., Kobayashi, A., Yokoyama, S., & Yamamoto, M. (2006) · Molecular Cell · doi:10.1016/j.molcel.2006.01.013 · Cited by 735 · cited 1×
“Contained within the Neh2 domain are 2 conserved motifs, DIDLID and ETGE, which are required for efficient binding with KEAP1 through interaction with its Kelch-repeat domain (21, 22).”
BackgroundExploring the Genomes of Cancer Cells: Progress and Promise
Stratton, M. R. (2011) · Science · doi:10.1126/science.1204040 · Cited by 711
SomaticSniper: identification of somatic point mutations in whole genome sequencing data
Larson, D. E., Harris, C. C., Chen, K., Koboldt, D. C., Abbott, T. E., Dooling, D. J., Ley, T. J., Mardis, E. R., Wilson, R. K., & Ding, L. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr665 · Cited by 658
Adam, J., Hatipoglu, E., O'Flaherty, L., Ternette, N., Sahgal, N., Lockstone, H., Baban, D., Nye, E., Stamp, G. W., Wolhuter, K., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.09.006 · Cited by 585
McMahon, M. J., Thomas, N., Itoh, K., Yamamoto, M. P., & Hayes, J. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m403061200 · Cited by 419
Ooi, A., Wong, J.-C., Petillo, D., Roossien, D., Perrier-Trudova, V., Whitten, D., Min, B. W. H., Tan, M.-H., Zhang, Z., Yang, X. J., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.08.024 · Cited by 401
Self-citationHeme oxygenase-1 induction by NRF2 requires inactivation of the transcriptional repressor BACH1
Reichard, J. F., Motz, G. T., & Puga, A. (2007) · Nucleic Acids Research · doi:10.1093/nar/gkm638 · Cited by 393
Sun, J., Brand, M., Zenke, Y., Tashiro, S., Groudine, M., & Igarashi, K. (2004) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0308083100 · Cited by 364
Kawai, Y., Garduño, L., Theodore, M., Yang, J., & Arinze, I. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m110.208173 · Cited by 362
MacLeod, A. K., McMahon, M. J., Plummer, S. M., Higgins, L. G., Penning, T. M., Igarashi, K., & Hayes, J. D. (2009) · Carcinogenesis · doi:10.1093/carcin/bgp176 · Cited by 305
Nrf2 mediates cancer protection but not prolongevity induced by caloric restriction
Pearson, K. J., Lewis, K. N., Price, N. L., Chang, J. W., Perez, E., Cascajo, M. V., Tamashiro, K. L., Poosala, S., Csiszár, A., Ungvari, Z. I., et al. (2008) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0712162105 · Cited by 238
Shibata, T., Kokubu, A., Saito, S., Narisawa-Saito, M., Sasaki, H., Aoyagi, K., Yoshimatsu, Y., Tachimori, Y., Kushima, R., Kiyono, T., et al. (2011) · Neoplasia · doi:10.1593/neo.11750 · Cited by 224
BRG1 Interacts with Nrf2 To Selectively Mediate HO-1 Induction in Response to Oxidative Stress
Zhang, J., Ohta, T., Maruyama, A., Hosoya, T., Nishikawa, K., Maher, J. M., Shibahara, S., Itoh, K., & Yamamoto, M. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00700-06 · Cited by 213
A mutation of Keap1 found in breast cancer impairs its ability to repress Nrf2 activity
Nioi, P., & Nguyen, T. (2007) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2007.08.051 · Cited by 212
Signal transduction events elicited by cancer prevention compounds
Kong, A. T., Yu, R., Hebbar, V., Chen, C., Owuor, E. D., Hu, R., Ee, P. L. R., & Mandlekar, S. (2001) · Mutation research. Fundamental and molecular mechanisms of mutagenesis · doi:10.1016/s0027-5107(01)00182-8 · Cited by 170
Shibata, T., Saito, S., Kokubu, A., Suzuki, T., Yamamoto, M. P., & Hirohashi, S. (2010) · Cancer Research · doi:10.1158/0008-5472.can-10-0384 · Cited by 133
Kinch, L. N., Grishin, N. V., & Brugarolas, J. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.10.005 · Cited by 109
Loignon, M., Miao, W., Hu, L., Bier, A., Bismar, T. A., Scrivens, P. J., Mann, K. K., Basik, M., Bouchard, A., Fiset, P., et al. (2009) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-08-1186 · Cited by 99
Ooi, A., & Furge, K. A. (2012) · 癌症：英文版 · doi:10.5732/cjc.012.10102 · Cited by 38
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Metadata
- Authors
- Ooi, A., Dykema, K., Ansari, A., Petillo, D., Snider, J., Kahnoski, R., Anema, J., Craig, D., Carpten, J., Teh, B.-T., & Furge, K. A.
- Affiliations
- Van Andel Institute (US)
- Venue
- Cancer Research
- Published
- 2013-04-01
- Volume
- 73
- Issue
- 7
- Pages
- 2044-2051
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2135514225
- Cited by
- 159
- References
- 35
- Citations by year
- 2026: 3 · 2025: 7 · 2024: 6 · 2023: 7 · 2022: 13 · 2021: 9 · 2020: 19 · 2019: 17 · 2018: 13 · 2017: 11 · 2016: 12 · 2015: 20 · 2014: 13 · 2013: 8
- FWCI
- 7.91
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics, phytochemicals, and oxidative stress
- Health Sciences › Medicine › Oncology › Renal cell carcinoma treatment
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Keywords
- papillary renal cell carcinoma, Nrf2 activation, CUL3, NRF2 mutation, SIRT1, fumarate hydratase, hereditary leiomyomatosis and renal cell carcinoma, somatic mutations, fumarate accumulation, tumor progression
- MeSH terms
- Kelch-Like ECH-Associated Protein 1, Amino Acid Sequence, Carcinoma, Renal Cell, Cells, Cultured, Humans, Immunoenzyme Techniques, Kidney Neoplasms, Kidney Tubules, Proximal, Molecular Sequence Data, Mutation, Phenotype, Biomarkers, Tumor, Blotting, Western, Sequence Homology, Amino Acid, Oligonucleotide Array Sequence Analysis, Gene Expression Profiling, Cullin Proteins, Intracellular Signaling Peptides and Proteins, NF-E2-Related Factor 2, Sirtuin 1, High-Throughput Nucleotide Sequencing
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