Targeting eIF4A-Dependent Translation of KRAS Signaling Molecules
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Abstract
Pancreatic adenocarcinoma (PDAC) epitomizes a deadly cancer driven by abnormal KRAS signaling. Here, we show that the eIF4A RNA helicase is required for translation of key KRAS signaling molecules and that pharmacological inhibition of eIF4A has single-agent activity against murine and human PDAC models at safe dose levels. EIF4A was uniquely required for the translation of mRNAs with long and highly structured 5′ untranslated regions, including those with multiple G-quadruplex elements. Computational analyses identified these features in mRNAs encoding KRAS and key downstream molecules. Transcriptome-scale ribosome footprinting accurately identified eIF4A-dependent mRNAs in PDAC, including critical KRAS signaling molecules such as PI3K, RALA, RAC2, MET, MYC, and YAP1. These findings contrast with a recent study that relied on an older method, polysome fractionation, and implicated redox-related genes as eIF4A clients. Together, our findings highlight the power of ribosome footprinting in conjunction with deep RNA sequencing in accurately decoding translational control mechanisms and define the therapeutic mechanism of eIF4A inhibitors in PDAC. Significance: These findings document the coordinate, eIF4A-dependent translation of RAS-related oncogenic signaling molecules and demonstrate therapeutic efficacy of eIF4A blockade in pancreatic adenocarcinoma.
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A synthetic eIF4A inhibitor, CR-1-31B, has shown potent activity against many cancer cell lines and promising efficacy in several mouse models.
“A synthetic eIF4A inhibitor, CR-1-31B, has shown potent activity against many cancer cell lines and promising efficacy in several mouse models (15, 17, 20, 21, 32, 33).”
From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [17]
The Results report activity of CR-1-31B in several mouse models of pancreatic cancer, including KPC tumors and a human patient-derived tumor model. The Figure 2 caption describes testing a panel of human pancreatic cancer cell lines, but our copy does not establish potent activity across many cancer cell lines more broadly. (LLM, conf=0.82)
Experimental — accuracy not yet measuredeIF4A-dependent mRNAs include key oncogenes such as MYC, BCL2, CDK6, KRAS, and YAP1, which are critical for tumorigenesis.
“Importantly, these mRNAs include key oncogenes such as MYC, BCL2, CDK6, KRAS, and YAP1 (15–17), which are critical for tumorigenesis.”
From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [17]
The Results report reduced KRAS, MYC, and YAP1 protein expression after eIF4A inhibition; the passage on eIF4A-dependent mRNAs also names MYC and YAP, and reports a reduction in KRAS translation efficiency. Our copy does not establish BCL2 or CDK6 as eIF4A-dependent mRNAs. Page numbers are unavailable in the indexed passages. (LLM, conf=0.86)
Experimental — accuracy not yet measuredeIF4A inhibitors target both isoforms, suppress translation of key oncogenes, and have demonstrated antitumor activity in a variety of cancers.
“eIF4A inhibitors, which target both isoforms, suppress translation of key oncogenes and have demonstrated antitumor activity in a variety of cancers (15, 17, 19–22).”
From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [17]
The Abstract and Results report suppressed translation of KRAS-signaling oncogenes and antitumor activity in mouse and human pancreatic-cancer models. The Introduction also describes promising results in leukemia and lymphoma models. The paper does not establish that the inhibitors target both eIF4A isoforms; its in vitro assay uses eIF4A1. (LLM, conf=0.88)
Experimental — accuracy not yet measuredThe RNA helicase component of eIF4F is required to unwind secondary structure in the 5′-UTR and initiate translation of mRNAs whose 5′-UTRs contain complex structures such as RNA G-quadruplexes.
“The RNA helicase component of this complex is required to unwind secondary structure in the 5′-UTR and initiate translation of mRNAs, specifically those RNAs whose 5′-UTRs contain complex structures such as RNA G-quadruplexes (15–17).”
From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [17]
Studies in mouse models of other cancers support the tolerability and efficacy of eIF4A inhibitors.
“Our results build on studies in mouse models of other cancers, including lymphoma, leukemia, breast, prostate, and pancreatic cancer, supporting the tolerability and efficacy of eIF4A inhibitors (15, 17, 20, 21, 38).”
From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [17]
eIF4A regulates YAP translation in pancreatic adenocarcinoma.
“eIF4A has also been shown to regulate YAP translation in pancreatic adenocarcinoma (17).”
From Targeting eIF4A-dependent translation in genetically complex sarcoma (2026) · cites this paper as [17]
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Cites
1 retracted
Csibi, A., Lee, G., Yoon, S.-O., Tong, H., Ilter, D., Elia, I., Fendt, S., Roberts, T. M., & Blenis, J. (2014) · Current Biology · doi:10.1016/j.cub.2014.08.007 · Cited by 253 · see citing works
RetractedMEME SUITE: tools for motif discovery and searching
Bailey, T. L., Boden, M., Buske, F. A., Frith, M., Grant, C. E., Clementi, L., Ren, J., Li, W. W., & Noble, W. S. (2009) · Nucleic Acids Research · doi:10.1093/nar/gkp335 · Cited by 10,648 · see citing works
FIMO: scanning for occurrences of a given motif
Grant, C. E., Bailey, T. L., & Noble, W. S. (2011) · Bioinformatics · doi:10.1093/bioinformatics/btr064 · Cited by 4,247 · see citing works
Genome-Wide Analysis in Vivo of Translation with Nucleotide Resolution Using Ribosome Profiling
Ingolia, N. T., Ghaemmaghami, S., Newman, J. R. S., & Weissman, J. S. (2009) · Science · doi:10.1126/science.1168978 · Cited by 3,853 · see citing works
Whole genomes redefine the mutational landscape of pancreatic cancer
Initiative, A. P. C. G., Waddell, N., Pajic, M., Patch, A.-M., Chang, D. K., Kassahn, K. S., Bailey, P., Johns, A. L., Miller, D., Nones, K., et al. (2015) · Nature · doi:10.1038/nature14169 · Cited by 2,642 · cited 2× · see citing works
“Genomic studies have catalogued the genetic drivers of PDAC and show nearly ubiquitous activation of KRAS and loss of tumor suppressor genes p53, p16/INK4A, and SMAD4 (13-17).”
BackgroundK-Ras(G12C) inhibitors allosterically control GTP affinity and effector interactions
Ostrem, J. M., Peters, U., Sos, M. L., Wells, J. A., & Shokat, K. M. (2013) · Nature · doi:10.1038/nature12796 · Cited by 2,557 · see citing works
Organoid models of human and mouse ductal pancreatic cancer
Boj, S. F., Hwang, C.-I., Baker, L. A., Chio, I. I. C., Engle, D. D., Corbo, V., Jager, M., Ponz-Sarvise, M., Tiriac, H., Spector, M. S., et al. (2015) · Cell · doi:10.1016/j.cell.2014.12.021 · Cited by 2,150 · see citing works
Self-citationPancreatic cancer genomes reveal aberrations in axon guidance pathway genes
Initiative, A. P. C. G., Biankin, A. V., Waddell, N., Kassahn, K. S., Gingras, M.-C., Muthuswamy, L. B., Johns, A. L., Miller, D. K., Wilson, P. J., Patch, A.-M., et al. (2012) · Nature · doi:10.1038/nature11547 · Cited by 2,058 · see citing works
Integrated genomic characterization of pancreatic ductal adenocarcinoma
Raphael, B. J., Hruban, R. H., Aguirre, A. J., Moffitt, R. A., Yeh, J. J., Stewart, C., Robertson, A. G., Cherniack, A. D., Gupta, M., Getz, G., et al. (2017) · Cancer Cell · doi:10.1016/j.ccell.2017.07.007 · Cited by 2,019 · see citing works
Genetics and biology of pancreatic ductal adenocarcinomaPreprint
Hezel, A. F., Kimmelman, A. C., Stanger, B. Z., Bardeesy, N. M., & DePinho, R. A. (2006) · Genes & Development · doi:10.1101/gad.1415606 · Cited by 1,570 · see citing works
Organoid Cultures Derived from Patients with Advanced Prostate Cancer
Gao, D., Vela, I., Sboner, A., Iaquinta, P. J., Karthaus, W. R., Gopalan, A., Dowling, C., Wanjala, J. N., Undvall, E. A., Arora, V. K., et al. (2014) · Cell · doi:10.1016/j.cell.2014.08.016 · Cited by 1,559 · see citing works
Holz, M. K., Ballif, B. A., Gygi, S. P., & Blenis, J. (2005) · Cell · doi:10.1016/j.cell.2005.10.024 · Cited by 1,262 · see citing works
Ingolia, N. T., Brar, G. A., Rouskin, S., McGeachy, A. M., & Weissman, J. S. (2012) · Nature Protocols · doi:10.1038/nprot.2012.086 · Cited by 1,240 · see citing works
From unwinding to clamping — the DEAD box RNA helicase family
Linder, P., & Jankowsky, E. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3154 · Cited by 1,177 · see citing works
Targeting KRAS mutant cancers with a covalent G12C-specific inhibitor
Janes, M. R., Zhang, J., Li, L.-S., Hansen, R., Peters, U., Guo, X., Chen, Y., Babbar, A., Firdaus, S. J., Darjania, L., et al. (2018) · Cell · doi:10.1016/j.cell.2018.01.006 · Cited by 1,172 · cited 1× · see citing works
“These include, inhibitors of G12C KRAS mutation (24-26), and strategies to co-target KRAS downstream signalling molecules like (e.”
BackgroundTargeting RAS–ERK signalling in cancer: promises and challenges
Samatar, A. A., & Poulikakos, P. I. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4281 · Cited by 1,163 · see citing works
KRAS: The Critical Driver and Therapeutic Target for Pancreatic Cancer
Waters, A. M., & Der, C. J. (2018) · Cold Spring Harbor Perspectives in Medicine · doi:10.1101/cshperspect.a031435 · Cited by 875 · see citing works
An RNA G-quadruplex in the 5′ UTR of the NRAS proto-oncogene modulates translation
Kumari, S., Bugaut, A., Huppert, J. L., & Balasubramanian, S. (2007) · Nature Chemical Biology · doi:10.1038/nchembio864 · Cited by 822 · see citing works
RAS Interaction with PI3K: More Than Just Another Effector Pathway
Castellano, E., & Downward, J. (2011) · Genes & Cancer · doi:10.1177/1947601911408079 · Cited by 762 · see citing works
Oncogenic Kras-induced GM-CSF production promotes the development of pancreatic neoplasia
Pylayeva-Gupta, Y., Lee, K. E., Hajdu, C. H., Miller, G., & Bar-Sagi, D. (2012) · Cancer Cell · doi:10.1016/j.ccr.2012.04.024 · Cited by 721 · see citing works
Combination of ERK and autophagy inhibition as a treatment approach for pancreatic cancer
Bryant, K. L., Stalnecker, C. A., Zeitouni, D., Klomp, J. E., Peng, S., Tikunov, A. P., Gunda, V., Pierobon, M., Waters, A. M., George, S. D., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0368-8 · Cited by 692 · see citing works
RNA G-quadruplexes cause eIF4A-dependent oncogene translation in cancer
Wolfe, A. L., Singh, K., Zhong, Y., Drewe, P., Rajasekhar, V. K., Sanghvi, V. R., Mavrakis, K. J., Jiang, M., Roderick, J. E., Van der Meulen, J., et al. (2014) · Nature · doi:10.1038/nature13485 · Cited by 635 · see citing works
Self-citationKinsey, C. G., Camolotto, S. A., Boespflug, A. M., Guillen, K. P., Foth, M., Truong, A., Schuman, S. S., Shea, J. E., Seipp, M. T., Yap, J. T., et al. (2019) · Nature Medicine · doi:10.1038/s41591-019-0367-9 · Cited by 634 · see citing works
Bardeesy, N. M., Aguirre, A. J., Chu, G. C., Cheng, K., Lopez, L. V., Hezel, A. F., Feng, B., Brennan, C. W., Weissleder, R., Mahmood, U., et al. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0601273103 · Cited by 575 · see citing works
Genetics and biology of pancreatic ductal adenocarcinoma
Ying, H., Dey, P., Yao, W., Kimmelman, A. C., Draetta, G. F., Maitra, A., & DePinho, R. A. (2016) · Genes & Development · doi:10.1101/gad.275776.115 · Cited by 527 · see citing works
RNA G-quadruplexes are globally unfolded in eukaryotic cells and depleted in bacteria
Guo, J. U., & Bartel, D. P. (2016) · Science · doi:10.1126/science.aaf5371 · Cited by 465 · see citing works
Winograd, R., Byrne, K. T., Evans, R. A., Odorizzi, P. M., Meyer, A. R. L., Bajor, D. L., Clendenin, C., Stanger, B. Z., Furth, E. E., Wherry, E. J., et al. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-14-0215 · Cited by 459 · see citing works
Pancreatic cancer biology and genetics from an evolutionary perspective
Makohon-Moore, A. P., & Iacobuzio–Donahue, C. A. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.66 · Cited by 430 · see citing works
rG4-seq reveals widespread formation of G-quadruplex structures in the human transcriptome
Kwok, C. K., Marsico, G., Sahakyan, A. B., Chambers, V. S., & Balasubramanian, S. (2016) · Nature Methods · doi:10.1038/nmeth.3965 · Cited by 426 · see citing works
NRF2 Promotes Tumor Maintenance by Modulating mRNA Translation in Pancreatic Cancer
Chio, I. I. C., Jafarnejad, S. M., Ponz-Sarvise, M., Park, Y., Rivera, K., Palm, W., Wilson, J., Sangar, V., Hao, Y., Öhlund, D., et al. (2016) · Cell · doi:10.1016/j.cell.2016.06.056 · Cited by 378 · cited 15× · see citing works
“Accordingly, PDACs show increased levels of mRNA translation and mediated through activation of MAPK, PI3K-AKTmTOR signals, NRF2, and MYC (18-20).”
BackgroundInfluentialTargeting the eIF4F Translation Initiation Complex: A Critical Nexus for Cancer Development
Pelletier, J., Graff, J., Ruggero, D., & Sonenberg, N. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-2789 · Cited by 367 · see citing works
Bordeleau, M.-È., Robert, F., Gerard, B., Lindqvist, L., Chen, S. M. H., Wendel, H., Brem, B., Greger, H., Lowe, S. W., Porco, J. A. J., et al. (2008) · Journal of Clinical Investigation · doi:10.1172/jci34753 · Cited by 335 · see citing works
Self-citationmRNA helicases: the tacticians of translational control
Parsyan, A., Svitkin, Y., Shahbazian, D., Gkogkas, C., Lasko, P., Merrick, W. C., & Sonenberg, N. (2011) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3083 · Cited by 323 · see citing works
Rocaglates convert DEAD-box protein eIF4A into a sequence-selective translational repressor
Iwasaki, S., Floor, S. N., & Ingolia, N. T. (2016) · Nature · doi:10.1038/nature17978 · Cited by 304 · see citing works
Antitumor Activity and Mechanism of Action of the Cyclopenta[b]benzofuran, Silvestrol
Cencic, R., Carrier, M., Galicia-Vázquez, G., Bordeleau, M.-E., Sukarieh, R., Bourdeau, A., Brem, B., Teodoro, J. G., Greger, H., Tremblay, M. L., et al. (2009) · PLoS ONE · doi:10.1371/journal.pone.0005223 · Cited by 302 · see citing works
Rubio, C. A., Weisburd, B., Holderfield, M., Arias, C., Fang, E., DeRisi, J. L., & Fanidi, A. (2014) · Genome Biology · doi:10.1186/s13059-014-0476-1 · Cited by 200 · see citing works
The Translation Inhibitor Rocaglamide Targets a Bimolecular Cavity between eIF4A and Polypurine RNA
Iwasaki, S., Iwasaki, W., Takahashi, M., Sakamoto, A., Watanabe, C., Shichino, Y., Floor, S. N., Fujiwara, K., Mito, M., Dodo, K., et al. (2018) · Molecular Cell · doi:10.1016/j.molcel.2018.11.026 · Cited by 193 · see citing works
RiboDiff: detecting changes of mRNA translation efficiency from ribosome footprints
田中, 義., Karaletsos, T., Drewe, P., Sreedharan, V. T., Kuo, D. C., Singh, K., Wendel, H., & Rätsch, G. (2016) · Bioinformatics · doi:10.1093/bioinformatics/btw585 · Cited by 171 · see citing works
Self-citationPolysome Fractionation to Analyze mRNA Distribution Profiles
Panda, A. C., Martindale, J. L., & Gorospe, M. (2017) · BIO-PROTOCOL · doi:10.21769/bioprotoc.2126 · Cited by 165 · see citing works
Gerard, B., Sangji, S., O’Leary, D. J., & Porco, J. A. J. (2006) · Journal of the American Chemical Society · doi:10.1021/ja062621j · Cited by 149 · see citing works
eIF3j is located in the decoding center of the human 40S ribosomal subunit.
Fraser, C., Berry, K. E., Hershey, J., & Doudna, J. (2007) · Molecules and Cells · doi:10.1016/j.molcel.2007.05.019 · Cited by 140 · see citing works
Gerard, B., Jones, G., & Porco, J. A. J. (2004) · Journal of the American Chemical Society · doi:10.1021/ja044798o · Cited by 138 · see citing works
Evidence for a Functionally Relevant Rocaglamide Binding Site on the eIF4A–RNA Complex
Sadlish, H., Galicia-Vázquez, G., PARIS, C. G., Aust, T., Bhullar, B., Chang, L., Helliwell, S. B., Hoepfner, D., Knapp, B., Riedl, R., et al. (2013) · ACS Chemical Biology · doi:10.1021/cb400158t · Cited by 127 · see citing works
Detecting RNA G-Quadruplexes (rG4s) in the TranscriptomePreprint
Kwok, C. K., Marsico, G., & Balasubramanian, S. (2018) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a032284 · Cited by 120 · see citing works
Enantioselective Synthesis of the Complex Rocaglate (−)‐Silvestrol
Gerard, B., Cencic, R., Pelletier, J., & Porco, J. A. J. (2007) · Angewandte Chemie International Edition · doi:10.1002/anie.200702707 · Cited by 118 · see citing works
Blasco, M. T., Navas, C., Martín-Serrano, G., Graña-Castro, O., Lechuga, C. G., Martín-Díaz, L., Djurec, M., Li, J., Morales-Cacho, L., Esteban-Burgos, L., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.03.002 · Cited by 115 · see citing works
Duplex Unwinding and ATPase Activities of the DEAD-Box Helicase eIF4A Are Coupled by eIF4G and eIF4B
Özeş, A., Feoktistova, K., Avanzino, B. C., & Fraser, C. S. (2011) · Journal of Molecular Biology · doi:10.1016/j.jmb.2011.08.004 · Cited by 114 · see citing works
eIF4A supports an oncogenic translation program in pancreatic ductal adenocarcinoma
Chan, K., Robert, F., Oertlin, C., Kapeller-Libermann, D., Avizonis, D., Gutierrez, J., Handly-Santana, A., Doubrovin, M., Park, J., Schoepfer, C., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-13086-5 · Cited by 106 · see citing works
Sen, N. D., Zhou, F., Harris, M. S., et al. (2016) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1612398113 · Cited by 104 · see citing works
Chu, J., Galicia-Vázquez, G., Cencic, R., Mills, J. R., Katigbak, A., Porco, J. A. J., & Pelletier, J. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.05.005 · Cited by 100 · see citing works
Rodrigo, C. M., Cencic, R., Roche, S. P., Pelletier, J., & Porco, J. A. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm201263k · Cited by 99 · see citing works
KRAS Protein Stability Is Regulated through SMURF2: UBCH5 Complex-Mediated β-TrCP1 Degradation
Shukla, S., Allam, U. S., Ahsan, A., Chen, G., Krishnamurthy, P. M., Marsh, K., Rumschlag, M., Shankar, S., Whitehead, C., Schipper, M., et al. (2014) · Neoplasia · doi:10.1593/neo.14184 · Cited by 96 · see citing works
Miglietta, G., Cogoi, S., Marinello, J., Capranico, G., Tikhomirov, A. S., Shchekotikhin, A. E., & Xodo, L. E. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.7b00622 · Cited by 92 · see citing works
Synthetic Silvestrol Analogues as Potent and Selective Protein Synthesis Inhibitors
Liu, T., Nair, S. J., Lescarbeau, A., Belani, J. D., Peluso, S., Conley, J., Tillotson, B. P., O’Hearn, P. J., Smith, S. A., Slocum, K. L., et al. (2012) · Journal of Medicinal Chemistry · doi:10.1021/jm3011542 · Cited by 86 · see citing works
Obligate Roles for p16 Ink4a and p19 Arf -p53 in the Suppression of Murine Pancreatic Neoplasia
Bardeesy, N. M., Morgan, J. A., Sinha, M., Signoretti, S., Srivastava, S., Loda, M. F., Merlino, G. T., & DePinho, R. A. (2002) · Molecular and Cellular Biology · doi:10.1128/mcb.22.2.635-643.2002 · Cited by 74 · see citing works
Real-time fluorescence assays to monitor duplex unwinding and ATPase activities of helicases
Özeş, A., Feoktistova, K., Avanzino, B. C., et al. (2014) · Nature Protocols · doi:10.1038/nprot.2014.112 · Cited by 56 · see citing works
Fujita-Sato, S., Galeas, J., Truitt, M., Pitt, C., Urisman, A., Bandyopadhyay, S., Ruggero, D., & McCormick, F. P. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-1623 · Cited by 54 · see citing works
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Crosstalk between G-quadruplex and ROS
Wu, S., Jiang, L., Lei, L., Fu, C., Huang, J., Hu, Y., Dong, Y., Chen, J., & Zeng, Q. (2023) · Cell Death & Disease · doi:10.1038/s41419-023-05562-0 · Cited by 69 · see citing works
“Furthermore, G4s also mediate the antioxidant process by forming stress granules and activating Nrf2, which is suggestive of their involvement in developing ROS-related diseases.”
BackgroundInfluentialCotargeting a MYC/eIF4A-survival axis improves the efficacy of KRAS inhibitors in lung cancer
Nardi, F., Perurena, N., Schade, A. E., Li, Z.-H., Ngo, K., Ivanova, E. V., Saldanha, A., Li, C., Gokhale, P. C., Hata, A. N., et al. (2023) · Journal of Clinical Investigation · doi:10.1172/jci167651 · Cited by 21 · see citing works
“E, CDK4), survival (e.g., MCL1, BCL-xL, BCL-2), transcription (e.g., YAP), metastasis (e.g., MMPs), angiogenesis (e.g., VEGF), immune recognition (e.g., PD-L1), and cell signaling (e.g., RAS, ERK, AKT, PI3K, MET, HER2) (14–16 , 23– 25).”
Targeting eIF4A-dependent translation in genetically complex sarcoma
Kim, Y.-M., Mohan, P., Sehrawat, U., Seffar, E., De Queiroz, R. M., Chadalavada, K., Persaud, N., Okada, T., Kulkarni, A., Lin, J., et al. (2026) · JCI Insight · doi:10.1172/jci.insight.192936
Self-citation
- Authors
- Singh, K., Lin, J., Lecomte, N., Mohan, P., Gokce, A., Sanghvi, V. R., Jiang, M., Grbovic-Huezo, O., Burčul, A., Stark, S. G., Romesser, P. B., Chang, Q., Melchor, J. P., Beyer, R. K., Duggan, M., Fukase, Y., Yang, G., Ouerfelli, O., Viale, A., de Stanchina, E., Stamford, A. W., Meinke, P. T., Rätsch, G., Leach, S. D., Ouyang, Z., & Wendel, H.-G.
- Affiliations
- Memorial Sloan Kettering Cancer Center (US)
- University of Connecticut (US)
- 4David M. Rubenstein Center for Pancreatic Cancer Research, Memorial Sloan-Kettering Cancer Center, New York, New York.
- Frederick National Laboratory for Cancer Research (US)
- 9Molecular Pharmacology Program, Memorial Sloan-Kettering Cancer Center, New York, New York.
- Dartmouth College (US)
- University of Massachusetts Amherst (US)
- Corresponding author
- Wendel, Hans-Guido
- ORCID
- Singh, Kamini
- Lin, Jianan
- Lecomte, Nicolas
- Mohan, Prathibha
- Sanghvi, Viraj R.
- Jiang, Man
- Grbovic-Huezo, Olivera
- Stark, Stefan G.
- Romesser, Paul B.
- Chang, Qing
- Melchor, Jerry P.
- Beyer, Rachel K.
- Fukase, Yoshiyuki
- Yang, Guangli
- Ouerfelli, Ouathek
- Viale, Agnes
- Stamford, Andrew W.
- Meinke, Peter T.
- Rätsch, Gunnar
- Leach, Steven D.
- Ouyang, Zhengqing
- Wendel, Hans-Guido
- Venue
- Cancer Research
- Published
- 2021-02-25
- Volume
- 81
- Issue
- 8
- Pages
- 2002-2014
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- PMC
- PMC8137674
- OpenAlex
- W3129229175
- Cited by
- 39
- References
- 57
- Citations by year
- 2026: 8 · 2025: 4 · 2024: 13 · 2023: 9 · 2022: 4 · 2021: 1
- FWCI
- 2.12
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- The Mouseion at the JAXlibrary (Jackson Laboratory) (submittedVersion)
- Funders
- NIH NCI Memorial Sloan Kettering Cancer Center (R01CA183876-03, R01 CA207217-04, R01CA190384-05, P50 CA217694-02, P50 CA192937-04)
- MSKCC Core Grant (P30 CA008748)
- NIH (R01CA204228, U54 OD020355-01, R35 GM124998)
- ETH Zürich (K12 CA184746)
- CCSG (P30 CA08748)
- NCI (P30 CA08748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA and protein synthesis mechanisms
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
- Keywords
- eIF4A, RNA helicase, pancreatic ductal adenocarcinoma, KRAS signaling, translation initiation, ribosome profiling, 5' untranslated region, G-quadruplex, translational regulation, phosphatidylinositol 3-kinase, RalA, Rac2, MET, c-Myc, YAP, polysome fractionation
- MeSH terms
- YAP-Signaling Proteins, RAC2 GTP-Binding Protein, Adenocarcinoma, Animals, Benzofurans, Cycloheximide, Humans, Mice, Nude, Mutation, Neoplasm Transplantation, Oxidation-Reduction, Pancreatic Neoplasms, Polyribosomes, Protein Synthesis Inhibitors, Genes, ras, Ribosomes, RNA, Messenger, Transcription Factors, Protein Biosynthesis, Triterpenes, Proto-Oncogene Proteins c-myc, Proto-Oncogene Proteins p21(ras), Sequence Analysis, RNA, Proto-Oncogene Proteins c-met, Phosphatidylinositol 3-Kinases, 5' Untranslated Regions, RNA Helicases, ral GTP-Binding Proteins, rac GTP-Binding Proteins, Eukaryotic Initiation Factor-4A, Cell Line, Tumor, Adaptor Proteins, Signal Transducing, Mice, G-Quadruplexes, Transcriptome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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