MAP kinase and autophagy pathways cooperate to maintain RAS mutant cancer cell survival
Open accessAbstract
Significance: Currently, there is no effective targeted therapy for oncogenic KRAS -driven cancer. We set out to identify RAS effector and stress response genes that critically support KRAS addiction, and therefore could serve as potential targets for KRAS mutant cancer. Using a combinatorial siRNA platform, we systematically interrogated the patterns of oncoeffector dependency in KRAS mutant and WT colorectal and pancreatic cancer cell lines and in normal cell lines. We found that RAF kinases are the major KRAS oncoeffectors and that cotargeting BRAF and CRAF kinases together with the autophagy E1 ligase ATG7 could efficiently eliminate KRAS mutant cells while minimizing toxicity in normal cells. Our work thus establishes a framework for the rational selection of target combinations for cancer treatment.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Genetic and pharmacological screens identified RTK signaling to PI3K and mTOR, and autophagy, as collateral dependencies with KRAS and MAPK pathway inhibitors.
“These experiments have identified receptor tyrosine kinase (RTK) signaling to PI3K and mTOR (23, 37–40), as well as the autophagy pathway (30) as collateral dependencies with KRAS and MAPK pathway inhibitors.”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [30]
In KRAS-mutant pancreatic cancer cells, the autophagy pathway acts as a collateral dependency alongside MAPK pathway inhibition.
“Recently, through combinatorial RNAi screens and hypothesis-driven approaches, we and others have identified the autophagy pathway as a collateral dependency partner with MAPK pathway inhibitors in pancreatic cancer cells with KRAS mutation (30, 95, 96).”
From KRAS mutation in pancreatic cancer (2021) · cites this paper as [30]
Three simultaneously published studies indicated that upon inhibition of the MAPK pathway, KRAS-mutant tumors depend on autophagy for survival.
“These studies indicated that upon the inhibition of the MAPK pathway, KRAS-mutant tumors depend on autophagy for survival”
From New Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness (2019) · cites this paper as [68]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Systematic RNA interference reveals that oncogenic KRAS-driven cancers require TBK1
Barbie, D. A., Tamayo, P., Boehm, J. S., Kim, S. Y., Moody, S. E., Dunn, I. F., Schinzel, A. C., Sandy, P., Meylan, E., Scholl, C., et al. (2009) · Nature · doi:10.1038/nature08460 · Cited by 3,869 · see citing works
Defining a Cancer Dependency Map
Tsherniak, A., Vazquez, F., Montgomery, P. G., Weir, B. A., Kryukov, G., Cowley, G. S., Gill, S., Harrington, W. F., Pantel, S., Krill-Burger, J. M., et al. (2017) · Cell · doi:10.1016/j.cell.2017.06.010 · Cited by 3,276 · see citing works
Drugging the undruggable RAS: Mission Possible?
Cox, A. D., Fesik, S. W., Kimmelman, A. C., Luo, J., & Der, C. J. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4389 · Cited by 1,997 · see citing works
Self-citationAn inhibitor of NEDD8-activating enzyme as a new approach to treat cancer
Soucy, T. A., Smith, P. G., Milhollen, M. A., Berger, A. J., Gavin, J. M., Adhikari, S., Brownell, J. E., Burke, K. E., Cardin, D. P., Critchley, S., et al. (2009) · Nature · doi:10.1038/nature07884 · Cited by 1,990 · see citing works
RAS oncogenes: weaving a tumorigenic web
Pylayeva-Gupta, Y., Grabocka, E., & Bar-Sagi, D. (2011) · Nature Reviews Cancer · doi:10.1038/nrc3106 · Cited by 1,789 · see citing works
Principles of cancer therapy: oncogene and non-oncogene addiction
Luo, J., Solimini, N. L., & Elledge, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.02.024 · Cited by 1,765 · see citing works
Self-citationEngelman, J. A., Chen, L., Tan, X., Crosby, K., Guimaraes, A. R., Upadhyay, R., Maira, M., McNamara, K., Perera, S. A., Song, Y., et al. (2008) · Nature Medicine · doi:10.1038/nm.1890 · Cited by 1,330 · see citing works
Activated Ras requires autophagy to maintain oxidative metabolism and tumorigenesis
Guo, J. Y., Chen, H.-Y., Mathew, R., Fan, J., Strohecker, A. M., Karsli-Uzunbas, G., Kamphorst, J. J., Chen, G., Lemons, J. M. S., Karantza, V., et al. (2011) · Genes & Development · doi:10.1101/gad.2016311 · Cited by 1,323 · see citing works
A Genome-wide RNAi Screen Identifies Multiple Synthetic Lethal Interactions with the Ras Oncogene
Luo, J., Emanuele, M. J., Li, D., Creighton, C. J., Schlabach, M. R., Westbrook, T. F., Wong, K.-K., & Elledge, S. J. (2009) · Cell · doi:10.1016/j.cell.2009.05.006 · Cited by 1,017 · see citing works
Self-citationGlucose Deprivation Contributes to the Development of <i>KRAS</i> Pathway Mutations in Tumor Cells
Yun, J., Rago, C., Cheong, I., Pagliarini, R., Angenendt, P., Rajagopalan, H., Schmidt, K., Willson, J. K. V., Markowitz, S., Zhou, S., et al. (2009) · Science · doi:10.1126/science.1174229 · Cited by 914 · see citing works
Autophagy and Tumor Metabolism
Kimmelman, A. C., & White, E. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.04.004 · Cited by 826 · see citing works
Stephen, A. G., Esposito, D., Bagni, R. K., & McCormick, F. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.02.017 · Cited by 795 · see citing works
Self-citationSelective inhibition of oncogenic KRAS output with small molecules targeting the inactive state
Patricelli, M. P., Janes, M. R., Li, L.-S., Hansen, R., Peters, U., Kessler, L. V., Chen, Y., Kucharski, J. M., Feng, J., Ely, T., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1105 · Cited by 759 · see citing works
Allele-specific inhibitors inactivate mutant KRAS G12C by a trapping mechanism
Lito, P., Solomon, M., Li, L.-S., Hansen, R., & Rosen, N. (2016) · Science · doi:10.1126/science.aad6204 · Cited by 691 · see citing works
McDonald, E. R., de Weck, A., Schlabach, M. R., Billy, E., Mavrakis, K. J., Hoffman, G. R., Belur, D., Castelletti, D., Frias, E., Gampa, K., et al. (2017) · Cell · doi:10.1016/j.cell.2017.07.005 · Cited by 658 · see citing works
MEK1 mutations confer resistance to MEK and B-RAF inhibition
Emery, C. M., Vijayendran, K. G., Zipser, M. C., Sawyer, A. M., Niu, L., Kim, J. J., Hatton, C., Chopra, R., Oberholzer, P. A., Karpova, M. B., et al. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0905833106 · Cited by 642 · see citing works
Wang, T., Yu, H., Hughes, N. W., Liu, B., Kendirli, A., Klein, K., Chen, W. W., Lander, E. S., & Sabatini, D. M. (2017) · Cell · doi:10.1016/j.cell.2017.01.013 · Cited by 632 · see citing works
Haigis, K. M., Kendall, K. R., Wang, Y., Cheung, A., Haigis, M. C., Glickman, J. N., Niwa-Kawakita, M., Sweet-Cordero, A., Sebolt-Leopold, J., Shannon, K. M., et al. (2008) · Nature Genetics · doi:10.1038/ng.115 · Cited by 610 · see citing works
Autophagy is required for glucose homeostasis and lung tumor maintenance
Karsli-Uzunbas, G., Guo, J. Y., Price, S., Teng, X., Laddha, S. V., Khor, S., Kalaany, N. Y., Jacks, T., Chan, C. S., Rabinowitz, J. D., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0363 · Cited by 560 · see citing works
Autophagy is critical for pancreatic tumor growth and progression in tumors with p53 alterations
Yang, A., Rajeshkumar, N. V., Wang, X., Yabuuchi, S., Alexander, B. M., Chu, G. C., Von Hoff, D. D., Maitra, A., & Kimmelman, A. C. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0362 · Cited by 486 · see citing works
Shimizu, T., Tolcher, A. W., Papadopoulos, K. P., Beeram, M., Rasco, D. W., Smith, L. S., Gunn, S., Smetzer, L., Mays, T. A., Kaiser, B., et al. (2012) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-11-2381 · Cited by 431 · see citing works
Corcoran, R. B., Cheng, K. A., Hata, A. N., Faber, A. C., Ebi, H., Coffee, E. M., Greninger, P., Brown, R. D., Godfrey, J. T., Cohoon, T. J., et al. (2013) · Cancer Cell · doi:10.1016/j.ccr.2012.11.007 · Cited by 377 · see citing works
Guo, J. Y., Teng, X., Laddha, S. V., Ma, S., Nostrand, S. C. V., Yang, Y., Khor, S., Chan, C. S., Rabinowitz, J. D., & White, E. (2016) · Genes & Development · doi:10.1101/gad.283416.116 · Cited by 373 · see citing works
Chien, Y., Kim, S., Bumeister, R., Loo, Y., Kwon, S. W., Johnson, C., Balakireva, M. G., Roméo, Y., Kopelovich, L., Gale, M., et al. (2006) · Cell · doi:10.1016/j.cell.2006.08.034 · Cited by 367 · see citing works
Cell cycle arrest mediated by the MEK/mitogen-activated protein kinase pathway
Pumiglia, K. M., & Decker, S. J. (1997) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.94.2.448 · Cited by 357 · see citing works
Blumenschein, G. R., Smit, E. F., Planchard, D., Kim, D.-W., Cadranel, J., De Pas, T., Dunphy, F., Udud, K., Ahn, M.-J., Hanna, N. H., et al. (2015) · Annals of Oncology · doi:10.1093/annonc/mdv072 · Cited by 349 · see citing works
Genetic analysis of Ras signalling pathways in cell proliferation, migration and survival
Drosten, M., Dhawahir, A., Sum, E. Y. M., Urosevic, J., Lechuga, C. G., Esteban, L. M., Castellano, E., Guerra, C., Santos, E., & Barbacid, M. (2010) · The EMBO Journal · doi:10.1038/emboj.2010.7 · Cited by 347 · see citing works
Jänne, P. A., van den Heuvel, M. M., Barlesi, F., Cobo, M., Mazieres, J., Crinò, L., Orlov, S., Blackhall, F., Wolf, J., Garrido, P., et al. (2017) · JAMA · doi:10.1001/jama.2017.3438 · Cited by 335 · see citing works
Bedard, P. L., Tabernero, J., Janku, F., Wainberg, Z. A., Paz-Ares, L., Vansteenkiste, J., Van Cutsem, E., Pérez-García, J., Stathis, A., Britten, C. D., et al. (2015) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1814 · Cited by 324 · see citing works
Role of the Kinase MST2 in Suppression of Apoptosis by the Proto-Oncogene Product Raf-1
O’Neill, E. E., Rushworth, L. K., Baccarini, M., & Kölch, W. (2004) · Science · doi:10.1126/science.1103233 · Cited by 317 · see citing works
Chen, J., Fujii, K., Zhang, L., Roberts, T. M., & Fu, H. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.141224398 · Cited by 316 · see citing works
MEK kinase activity is not necessary for Raf‐1 function
Hüser, M., Luckett, J., Chiloeches, A., Mercer, K., Iwobi, M., Giblett, S., Sun, X., Brown, J., Marais, R., & Pritchard, C. A. (2001) · The EMBO Journal · doi:10.1093/emboj/20.8.1940 · Cited by 310 · see citing works
Blasco, R. B., Francoz, S., Santamaría, D., Cañamero, M., Dubus, P., Charron, J., Baccarini, M., & Barbacid, M. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.04.002 · Cited by 302 · see citing works
Stem Cell Depletion Through Epidermal Deletion of Rac1
Benitah, S. A., Frye, M., Glogauer, M., & Watt, F. M. (2005) · Science · doi:10.1126/science.1113579 · Cited by 249 · see citing works
Functional identification of optimized RNAi triggers using a massively parallel Sensor assay
Fellmann, C., Zuber, J., McJunkin, K., Chang, K., Malone, C., Dickins, R., Xu, Q.-K., Hengartner, M., Elledge, S., Hannon, G., et al. (2011) · Molecules and Cells · doi:10.1016/j.molcel.2011.02.008 · Cited by 233 · see citing works
Self-citationProbing the roles of SUMOylation in cancer cell biology by using a selective SAE inhibitor
He, X., Riceberg, J., Soucy, T. A., Koenig, E. M., Minissale, J., Gallery, M. A., Bernard, H., Yang, X., Liao, H., Rabino, C., et al. (2017) · Nature Chemical Biology · doi:10.1038/nchembio.2463 · Cited by 230 · see citing works
Macroautophagy is dispensable for growth of KRAS mutant tumors and chloroquine efficacy
Eng, C. H., Wang, Z., Tkach, D., Toral‐Barza, L., Ugwonali, S., Liu, S., Fitzgerald, S., George, E., Frias, E., Cochran, N. R., et al. (2015) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1515617113 · Cited by 228 · see citing works
<i>Atg7</i> Overcomes Senescence and Promotes Growth of <i>Braf</i> V600E-Driven Melanoma
Xie, X., Koh, J. Y., Price, S., White, E., & Mehnert, J. M. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-1473 · Cited by 208 · see citing works
Effects of Raf Dimerization and Its Inhibition on Normal and Disease-Associated Raf Signaling
Freeman, A. K., Ritt, D. A., & Morrison, D. K. (2013) · Molecular Cell · doi:10.1016/j.molcel.2012.12.018 · Cited by 201 · see citing works
Kim, H. S., Mendiratta, S., Kim, J., Pecot, C. V., Larsen, J. E., Zubovych, I., Seo, B. Y., Kim, J., Eskiocak, B., Chung, H., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.041 · Cited by 172 · see citing works
Requirement for Rac1 in a K-ras–Induced Lung Cancer in the Mouse
Kissil, J. L., Walmsley, M. J., Hanlon, L., Haigis, K. M., Kim, C. F. B., Sweet-Cordero, A., Eckman, M. S., Tuveson, D. A., Capobianco, A. J., Tybulewicz, V. L. J., et al. (2007) · Cancer Research · doi:10.1158/0008-5472.can-07-2300 · Cited by 167 · see citing works
Tolcher, A. W., Patnaik, A., Papadopoulos, K. P., Rasco, D. W., Becerra, C. R., Allred, A. J., Orford, K., Aktan, G., Ferron-Brady, G., Ibrahim, N., et al. (2015) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-014-2615-5 · Cited by 158 · see citing works
Differential effector engagement by oncogenic KRAS
Yuan, T. L., Amzallag, A., Bagni, R., Yi, M., Afghani, S., Burgan, W., Fer, N., Strathern, L. A., Powell, K., Smith, B., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.051 · Cited by 150 · see citing works
Self-citationC-Raf Is Required for the Initiation of Lung Cancer by K-RasG12D
Karreth, F. A., Frese, K. K., DeNicola, G. M., Baccarini, M., & Tuveson, D. A. (2011) · Cancer Discovery · doi:10.1158/2159-8290.cd-10-0044 · Cited by 149 · see citing works
Combined MEK and PI3K Inhibition in a Mouse Model of Pancreatic Cancer
Alagesan, B., Contino, G., Guimarães, A. R., Corcoran, R. B., Deshpande, V., Wojtkiewicz, G. R., Hezel, A. F., Wong, K., Loda, M. F., Weissleder, R., et al. (2014) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-14-1591 · Cited by 145 · see citing works
Scholl, F. A., Dumesic, P. A., Barragan, D. I., Harada, K., Bissonauth, V., Charron, J., & Khavari, P. A. (2007) · Developmental Cell · doi:10.1016/j.devcel.2007.03.009 · Cited by 142 · see citing works
Early Requirement of Rac1 in a Mouse Model of Pancreatic Cancer
Heid, I., Lubeseder–Martellato, C., Sipos, B., Mazur, P. K., Lesina, M., Schmid, R. M., & Siveke, J. T. (2011) · Gastroenterology · doi:10.1053/j.gastro.2011.04.043 · Cited by 139 · see citing works
Do, K. T., Speranza, G., Bishop, R. J., Khin, S. A., Rubinstein, L., Kinders, R. J., Datiles, M. B., Eugeni, M. A., Lam, M. H., Doyle, L. A., et al. (2015) · Investigational New Drugs · doi:10.1007/s10637-015-0212-z · Cited by 133 · see citing works
Guo, J. Y., & White, E. (2013) · Autophagy · doi:10.4161/auto.26123 · Cited by 125 · see citing works
Role of Phosphoinositide 3-Kinase Regulatory Isoforms in Development and Actin Rearrangement
Brachmann, S. M., Yballe, C. M., Innocenti, M., Deane, J. A., Fruman, D. A., Thomas, S. Μ., & Cantley, L. C. (2005) · Molecular and Cellular Biology · doi:10.1128/mcb.25.7.2593-2606.2005 · Cited by 123 · see citing works
Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis
Wojnowski, L., Stancato, L. F., Larner, A. C., et al. (2000) · Mechanisms of Development · doi:10.1016/s0925-4773(99)00276-2 · Cited by 120 · see citing works
Sanclemente, M., Francoz, S., Esteban-Burgos, L., Bousquet-Mur, E., Djurec, M., Lopez-Casas, P. P., Hidalgo, M., Guerra, C., Drosten, M., Musteanu, M., et al. (2018) · Cancer Cell · doi:10.1016/j.ccell.2017.12.014 · Cited by 119 · see citing works
C911: A Bench-Level Control for Sequence Specific siRNA Off-Target Effects
Buehler, E., Chen, Y.-C., & Martin, S. (2012) · PLoS ONE · doi:10.1371/journal.pone.0051942 · Cited by 116 · see citing works
Development of siRNA Payloads to Target <i>KRAS</i> -Mutant Cancer
Yuan, T. L., Fellmann, C., Lee, C.-S., Ritchie, C. D., Thapar, V., Lee, L. C., Hsu, D. J., Grace, D., Carver, J. O., Zuber, J., et al. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-13-0900 · Cited by 113 · see citing works
Self-citationHerrera, R., Hubbell, S. E., Decker, S. J., & Petruzzelli, L. (1998) · Experimental Cell Research · doi:10.1006/excr.1997.3847 · Cited by 99 · see citing works
Wainberg, Z. A., Alsina, M., Soares, H. P., Braña, I., Britten, C. D., Del Conte, G., Ezeh, P., Houk, B., Kern, K. A., Leong, S., et al. (2017) · Targeted Oncology · doi:10.1007/s11523-017-0530-5 · Cited by 98 · see citing works
A Role for Mitochondrial Translation in Promotion of Viability in K-Ras Mutant Cells
Martin, T. D., Cook, D. R., Choi, M. Y., Li, M. Z., Haigis, K. M., & Elledge, S. J. (2017) · Cell Reports · doi:10.1016/j.celrep.2017.06.061 · Cited by 89 · see citing works
Raf-1 sets the threshold of Fas sensitivity by modulating Rok-α signaling
Piazzolla, D., Meissl, K., Kučerová, L., Rubiolo, C., & Baccarini, M. (2005) · The Journal of Cell Biology · doi:10.1083/jcb.200504137 · Cited by 84 · see citing works
Peschard, P., McCarthy, A., Leblanc-Dominguez, V., Yeo, M., Guichard, S., Stamp, G., & Marshall, C. J. (2012) · Current Biology · doi:10.1016/j.cub.2012.09.013 · Cited by 82 · see citing works
Grilley-Olson, J. E., Bedard, P. L., Fasolo, A., Cornfeld, M., Cartee, L., Razak, A. R. A., Stayner, L.-A., Wu, Y., Greenwood, R., Singh, R., et al. (2016) · Investigational New Drugs · doi:10.1007/s10637-016-0377-0 · Cited by 81 · see citing works
Self-citationSurvivin depletion preferentially reduces the survival of activated K-Ras-transformed cells
Sarthy, A. V., Morgan-Lappe, S. E., Zakula, D., Vernetti, L. A., Schurdak, M. E., Packer, J. C. L., Anderson, M. G., Shirasawa, S., Sasazuki, T., & Fesik, S. W. (2007) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-06-0560 · Cited by 78 · see citing works
Weng, M., Lee, J., Wei, S., Li, Q., Shahamatdar, S., Hsu, D. J., Schetter, A. J., Swatkoski, S., Mannan, P., Garfield, S. H., et al. (2012) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1207673110 · Cited by 66 · see citing works
Self-citationCovalent Guanosine Mimetic Inhibitors of G12C KRAS
Xiong, Y., Lu, J., Hunter, J., Li, L., Scott, D., Choi, H. G., Lim, S. M., Manandhar, A., Gondi, S., Sim, T., et al. (2017) · ACS Medicinal Chemistry Letters · doi:10.1021/acsmedchemlett.6b00373 · Cited by 66 · see citing works
Defining Key Signaling Nodes and Therapeutic Biomarkers in NF1 -Mutant Cancers
Malone, C. F., Longo, J. F., Maertens, O., Raedt, T. D., Ingraham, R., & Cichowski, K. M. (2014) · Cancer Discovery · doi:10.1158/2159-8290.cd-14-0159 · Cited by 65 · see citing works
Dorard, C., Estrada, C., Barbotin, C., Larcher, M., Garancher, A., Leloup, J., Beermann, F., Baccarini, M., Pouponnot, C., Larue, L., et al. (2017) · Nature Communications · doi:10.1038/ncomms15262 · Cited by 55 · see citing works
Nishiguchi, G., Rico, A. C., Tanner, H. R., Aversa, R. J., Taft, B. R., Subramanian, S., Setti, L., Burger, M. T., Wan, L., Tamez, V., et al. (2017) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.6b01862 · Cited by 46 · see citing works
Shao, W., Mishina, Y. M., Feng, Y., Caponigro, G., Cooke, V. G., Rivera, S., Wang, Y., Shen, F., Korn, J. M., Griner, L. A. M., et al. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2033 · Cited by 44 · see citing works
RAS Signalling Is Abnormal in a c- raf1 MEK1 Double Mutant
Bottorff, D. A., Stang, S. L., Agellon, S., & Stone, J. C. (1995) · Molecular and Cellular Biology · doi:10.1128/mcb.15.9.5113 · Cited by 29 · see citing works
Garimella, S. V., Gehlhaus, K., Dine, J. L., Pitt, J. J., Grandin, M., Chakka, S., Nau, M. M., Caplen, N. J., & Lipkowitz, S. (2014) · Breast Cancer Research · doi:10.1186/bcr3645 · Cited by 28 · see citing works
Self-citationThe Nuclear Translocation of ERK
Berti, D. A., & Seger, R. (2016) · Methods in molecular biology · doi:10.1007/978-1-4939-6424-6_13 · Cited by 28 · see citing works
Rationale for RAS Mutation-Tailored Therapies
Montalvo, S. K., Li, L., & Westover, K. D. (2016) · Future Oncology · doi:10.2217/fon-2016-0363 · Cited by 15 · see citing works
Smith, J. L., Lee, L. C., Read, A., Li, Q., Yu, B., Lee, C.-S., & Luo, J. (2016) · Cell & Bioscience · doi:10.1186/s13578-016-0122-6 · Cited by 14 · see citing works
Self-citation
Flagged first, then by citations
Cited by
Sorted by citations
KRAS mutation in pancreatic cancer
Luo, J. (2021) · Seminars in Oncology · doi:10.1053/j.seminoncol.2021.02.003 · Cited by 360 · see citing works
Self-citationThe metabolic landscape of RAS-driven cancers from biology to therapy
Mukhopadhyay, S., Vander Heiden, M. G., & McCormick, F. (2021) · Nature Cancer · doi:10.1038/s43018-021-00184-x · Cited by 315 · see citing works
Self-citationNew Horizons in KRAS-Mutant Lung Cancer: Dawn After Darkness
Yang, H., Liang, S.-Q., Schmid, R. A., & Peng, R.-W. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.00953 · Cited by 129 · see citing works
Ravichandran, M., Hu, J., Cai, C., Ward, N. P., Venida, A., Foakes, C., Kuljanin, M., Yang, A., Hennessey, C. J., Yang, Y., et al. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0044 · Cited by 80 · see citing works
Targeting autophagy as a therapeutic strategy against pancreatic cancer
Yamamoto, K., Iwadate, D., Kato, H., Nakai, Y., Tateishi, K., & Fujishiro, M. (2022) · Journal of Gastroenterology · doi:10.1007/s00535-022-01889-1 · Cited by 29 · see citing works
- Authors
- Lee, C.-S., Lee, L. C., Yuan, T. L., Chakka, S., Fellmann, C., Lowe, S. W., Caplen, N. J., McCormick, F., & Luo, J.
- Affiliations
- National Cancer Institute (US)
- University of California, San Francisco (US)
- Cold Spring Harbor Laboratory (US)
- Memorial Sloan Kettering Cancer Center (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-02
- Volume
- 116
- Issue
- 10
- Pages
- 4508-4517
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6410784
- OpenAlex
- W2913634791
- Cited by
- 126
- References
- 72
- Citations by year
- 2026: 4 · 2025: 11 · 2024: 14 · 2023: 22 · 2022: 14 · 2021: 26 · 2020: 21 · 2019: 14
- FWCI
- 6.21
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Cold Spring Harbor Laboratory Institutional Repository (Cold Spring Harbor Laboratory) (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (ZIABC011437, T32CA108462, P30CA008748)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Melanoma and MAPK Pathways
- Health Sciences › Medicine › Epidemiology › Autophagy in Disease and Therapy
- Keywords
- KRAS mutation, MAPK signaling, autophagy, Raf kinase, BRAF, Raf-1, ATG7, colorectal cancer, pancreatic cancer, combination therapy, siRNA screen, tumor cell survival
- MeSH terms
- Autophagic Cell Death, Cell Survival, Humans, Pancreatic Neoplasms, Colorectal Neoplasms, Proto-Oncogene Proteins p21(ras), Caco-2 Cells, MAP Kinase Signaling System, HCT116 Cells, Extracellular Signal-Regulated MAP Kinases
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 ›
Are you an author, or do you see a problem with this page? Request a review
