Proteogenomic Network Analysis of Context-Specific KRAS Signaling in Mouse-to-Human Cross-Species Translation
Open accessAbstract
The highest frequencies of KRAS mutations occur in colorectal carcinoma (CRC) and pancreatic ductal adenocarcinoma (PDAC). The ability to target downstream pathways mediating KRAS oncogenicity is limited by an incomplete understanding of the contextual cues modulating the signaling output of activated K-RAS. We performed mass spectrometry on mouse tissues expressing wild-type or mutant Kras to determine how tissue context and genetic background modulate oncogenic signaling. Mutant Kras dramatically altered the proteomes and phosphoproteomes of preneoplastic and neoplastic colons and pancreases in a context-specific manner. We developed an approach to statistically humanize the mouse networks with data from human cancer and identified genes within the humanized CRC and PDAC networks synthetically lethal with mutant KRAS. Our studies demonstrate the context-dependent plasticity of oncogenic signaling, identify non-canonical mediators of KRAS oncogenicity within the KRAS-regulated signaling network, and demonstrate how statistical integration of mouse and human datasets can reveal cross-species therapeutic insights.
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Mutant forms of KRAS produce distinct molecular and cellular phenotypes that are largely dependent upon the tissue context.
“mutant forms of KRAS produce distinct molecular and cellular phenotypes that are largely dependent upon the tissue context4,78,79”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [78]
The intrinsic biochemical properties of a KRAS mutant are likely maintained in each cancer, but their downstream signaling properties, and ultimately their effects on tumorigenesis, are determined by the basal configuration of the tissue-specific signaling network.
“the intrinsic biochemical properties of a KRAS mutant are likely maintained in each cancer, their downstream signaling properties, and ultimately their effects on tumorigenesis, are determined by the basal configuration of the tissue-specific signaling network78”
From The origins and genetic interactions of KRAS mutations are allele- and tissue-specific (2021) · cites this paper as [78]
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“14*10−2) as conserved KrasG12D responsive pathways (Thomas et al., 2003; Thomas et al., 2006).”
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BackgroundMethodKRAS Alleles: The Devil Is in the Detail
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“Missense substitutions in the KRAS gene, which encodes a monomeric GTPase, activate KRAS protein by inhibiting its ability to hydrolyze GTP or by promoting the rapid exchange of GDP for GTP (Haigis, 2017).”
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BackgroundOptimally weighted Z-test is a powerful method for combining probabilities in meta-analysis
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Self-citationKRAS G12D Mutation Subtype Is A Prognostic Factor for Advanced Pancreatic Adenocarcinoma
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“In PDAC, KRASG12D is associated with shorter overall survival and poorer prognosis than other forms of KRAS (Bournet et al., 2016).”
BackgroundTissue-Specific Oncogenic Activity of KRASA146T
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BackgroundResultSelf-citationOncogenic <i>Kras</i> drives invasion and maintains metastases in colorectal cancer
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BackgroundMutant KRAS as a critical determinant of the therapeutic response of colorectal cancer
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“EPHA2 overexpression correlates with poor prognosis in other cancers and is a potential therapeutic target (Song et al., 2017; Tandon et al., 2011).”
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MethodNDEx 2.0: A Clearinghouse for Research on Cancer Pathways
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MethodMicroRNA-34b Inhibits Pancreatic Cancer Metastasis Through Repressing Smad3
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BackgroundMouse Genome Informatics (MGI): reflecting on 25 years
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MethodBrandes, F., Schmidt, K. M., Wagner, C., Redekopf, J., Schlitt, H. J., Geissler, E. K., & Lang, S. A. (2015) · BMC Cancer · doi:10.1186/s12885-015-1064-9 · Cited by 51 · cited 1× · see citing works
“Inhibition of MET – the most therapeutically tractable of these four potential targets – has shown efficacy in preclinical PDAC models (Brandes et al., 2015), but results in severe toxicity in patients in combination with standard-of-care (Zhen et Brubaker et al.”
BackgroundA phase I trial of cabozantinib and gemcitabine in advanced pancreatic cancer
Zhen, D. B., Griffith, K. A., Ruch, J. M., Camphausen, K. A., Savage, J. E., Kim, E. J.-H., Sahai, V., Simeone, D. M., & Zalupski, M. M. (2016) · Investigational New Drugs · doi:10.1007/s10637-016-0376-1 · Cited by 39 · see citing works
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“Kinase enrichment analysis on the phosphoproteomics data was performed using the GSEA software and kinase-substrate “gene sets” assembled from PhosphositePlus as previously described (Hornbeck et al., 2015; Lyons et al., 2018).”
MethodSelf-citationState of the art biological therapies in pancreatic cancer
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Silencing of argininosuccinate lyase inhibits colorectal cancer formation
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BackgroundMARCKS as a Negative Regulator of Lipopolysaccharide Signaling
Manček‐Keber, M., Benčina, M., Japelj, B., Panter, G., Andrä, J., Brandenburg, K., Triantafilou, M., Triantafilou, K., & Jerala, R. (2012) · The Journal of Immunology · doi:10.4049/jimmunol.1003605 · Cited by 24 · cited 1× · see citing works
“The CDK2 subnetwork linked MARCKS dephosphorylation to activation of TNFA Signaling via NFKB, consistent with MARCKS function as a negative regulator of inflammatory signaling (Mancek-Keber et al., 2012).”
BackgroundRegulation of homeostasis and oncogenesis in the intestinal epithelium by Ras
Velho, S., & Haigis, K. M. (2011) · Experimental Cell Research · doi:10.1016/j.yexcr.2011.06.002 · Cited by 18 · cited 1× · see citing works
“The failure to inhibit K-RAS has motivated the search for alternative therapeutic strategies targeting its downstream signaling effectors (Simanshu et al., 2017; Velho and Haigis, 2011).”
BackgroundSelf-citationBasilico, C., Modica, C., Maione, F., Vigna, E., & Comoglio, P. M. (2018) · International Journal of Cancer · doi:10.1002/ijc.31550 · Cited by 14 · cited 1× · see citing works
“SMAD3 and MET have been implicated in metastatic pancreatic cancer (Basilico et al., 2018; Liu et al., 2013).”
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Towards targeting of shared mechanisms of cancer metastasis and therapy resistance
Weiß, F., Lauffenburger, D. A., & Friedl, P. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-021-00427-0 · Cited by 294 · see citing works
Self-citationThe origins and genetic interactions of KRAS mutations are allele- and tissue-specific
Cook, J. H., Melloni, G. E. M., Gulhan, D. C., Park, P. J., & Haigis, K. M. (2021) · Nature Communications · doi:10.1038/s41467-021-22125-z · Cited by 208 · see citing works
Self-citationNext batter up! Targeting cancers with KRAS-G12D mutations
Zeissig, M. N., Ashwood, L. M., Kondrashova, O., & Sutherland, K. D. (2023) · Trends in Cancer · doi:10.1016/j.trecan.2023.07.010 · Cited by 128 · see citing works
Classification of KRAS -Activating Mutations and the Implications for Therapeutic Intervention
Johnson, C. W., Burkhart, D. L., & Haigis, K. M. (2022) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-0035 · Cited by 130 · see citing works
Self-citationTranslating preclinical models to humans
Brubaker, D. K., & Lauffenburger, D. A. (2020) · Science · doi:10.1126/science.aay8086 · Cited by 124 · see citing works
Self-citationDiscovery of a selective inhibitor of doublecortin like kinase 1
Ferguson, F. M., Nabet, B., Raghavan, S., Liu, Y., Leggett, A. L., Kuljanin, M., Kalekar, R. L., Yang, A., He, S., Wang, J., et al. (2020) · Nature Chemical Biology · doi:10.1038/s41589-020-0506-0 · Cited by 109 · see citing works
Self-citationCell Type–Specific Adaptive Signaling Responses to KRASG12C Inhibition
Solanki, H. S., Welsh, E. A., Fang, B., Izumi, V., Darville, L., Stone, B., Franzese, R., Chavan, S., Kinose, F., Imbody, D., et al. (2021) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-20-3872 · Cited by 106 · see citing works
“These results, along with signaling studies of tissues from KRASmutant genetically engineeredmousemodels (GEMMs), argue strongly that cell context will dictate responses to KRAS inhibition (42).”
ResultLi, H., Su, Q., Li, B., Lan, L., Wang, C., Li, W., Wang, G., Chen, W., He, Y., & Zhang, C. (2020) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.15104 · Cited by 107 · see citing works
Soltis, A. R., Bateman, N. W., Liu, J., Nguyen, T. M., Franks, T. J., Zhang, X., Dalgard, C. L., Viollet, C., Somiari, S., Yan, C., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100819 · Cited by 76 · see citing works
Rocca, A., Braga, L., Volpe, M. C., Maiocchi, S., & Generali, D. (2022) · Cancers · doi:10.3390/cancers14215306 · Cited by 65 · see citing works
“However, the signaling pattern specific for each KRAS mutant is affected by the tumor tissue of origin [35] and by the coexisting mutations and other molecular alterations [36], preventing a simple predictive algorithm.”
BackgroundEPHA2-dependent outcompetition of KRASG12D mutant cells by wild-type neighbors in the adult pancreas
Hill, W., Ζαραγκούλιας, Α., Salvador-Barberó, B., Parfitt, G. J., Alatsatianos, M., Padilha, A., Porazinski, S. R., Woolley, T. E., Morton, J. P., Sansom, O. J., et al. (2021) · Current Biology · doi:10.1016/j.cub.2021.03.094 · Cited by 56 · see citing works
A proteomic and phosphoproteomic landscape of KRAS mutant cancers identifies combination therapies
Liu, Z., Liu, Y., Qian, L., Jiang, S., Gai, X., Ye, S., Chen, Y., Wang, X., Zhai, L., Xu, J. Q., et al. (2021) · Molecular Cell · doi:10.1016/j.molcel.2021.07.021 · Cited by 54 · see citing works
Integrated multi-omics characterization of KRAS mutant colorectal cancer
Chong, W., Zhu, X., Ren, H., Ye, C., Xu, K., Wang, Z., Jia, S., Shang, L., Li, L., & Chen, H. (2022) · Theranostics · doi:10.7150/thno.73089 · Cited by 53 · see citing works
“Given that the phosphorylation cascade dominates KRAS-induced downstream signaling, obtaining a comprehensive profile of the proteome and phosphoproteome will be particularly informative to improve our understanding of the phenotypic heterogeneity of KRAS-mutant cancers [19, 20].”
BackgroundTargeting KRAS G12C Mutation in Colorectal Cancer, A Review: New Arrows in the Quiver
Ros, J., Vaghi, C., Baraibar, I., Gonzalez, N. S., Rodríguez-Castells, M., García, A., Alcaráz, A., Salvà, F., Tabernero, J. M., & Élez, E. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25063304 · Cited by 50 · see citing works
“KRAS G12D mutations have been shown to elicit distinct gene and protein expression profiles compared with other KRAS mutations in a tissue-specific manner [15,16].”
BackgroundBrubaker, D. K., Kumar, M. P., Chiswick, E. L., Gregg, C., Starchenko, A., Vega, P. N., Southard-Smith, A. N., Simmons, A. J., Scoville, E., Coburn, L. A., et al. (2020) · Science Signaling · doi:10.1126/scisignal.aay3258 · Cited by 45 · see citing works
Self-citationRicciuti, B., Son, J., Okoro, J. J., Mira, A., Patrucco, E., Eum, Y., Wang, X., Paranal, R., Wang, H., Lin, M., et al. (2022) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-21-2719 · Cited by 42 · see citing works
Behind the Wheel of Epithelial Plasticity in KRAS-Driven Cancers
Arner, E. N., Du, W., & Brekken, R. A. (2019) · Frontiers in Oncology · doi:10.3389/fonc.2019.01049 · Cited by 38 · see citing works
“(4) developed a statistical approach to humanize multiplexed quantitative proteomic data from mouse models of colon and pancreatic cancer.”
BackgroundThe transcriptional landscape of glycosylation-related genes in cancer
Rodríguez, E., Lindijer, D., van Vliet, S. J., García-Vallejo, J. J., & van Kooyk, Y. (2024) · iScience · doi:10.1016/j.isci.2024.109037 · Cited by 36 · see citing works
Are Parallel Proliferation Pathways Redundant?
Nussinov, R., Tsai, C., & Jang, H. (2020) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2020.03.013 · Cited by 33 · see citing works
Identification of a targetable KRAS-mutant epithelial population in non-small cell lung cancer
Maroni, G., Bassal, M. A., Krishnan, I., Fhu, C. W., Savova, V., Žilionis, R., Maymi, V. A., Pandell, N., Csizmadia, E., Zhang, J., et al. (2021) · Communications Biology · doi:10.1038/s42003-021-01897-6 · Cited by 29 · see citing works
Ras isoform-specific expression, chromatin accessibility, and signaling
Nussinov, R., Zhang, M., Maloney, R., & Jang, H. (2021) · Biophysical Reviews · doi:10.1007/s12551-021-00817-6 · Cited by 28 · see citing works
“Taken together, KRas and NRas can be differentially expressed in specific cell types because their chromatin accessibility status differ (Brubaker et al. 2019).”
BackgroundKrasP34R and KrasT58I mutations induce distinct RASopathy phenotypes in mice
Wong, J. C. Y., Pérez-Mancera, P. A., Huang, T. Q., Kim, J., Grego‐Bessa, J., Alzamora, M. D. P., Kogan, S. C., Sharir, A., Keefe, S. H., Morales, C. E., et al. (2020) · JCI Insight · doi:10.1172/jci.insight.140495 · Cited by 24 · see citing works
“differences in the lung phenotypes among WT, KrasT58I/+, and CMV-Cre KrasLSL-P34R/+ pups might be due to failure to appropriately modulate ERK activity during the sacculation phase of lung development (Figure 5B) (24, 25).”
BackgroundMyers, P. J., Lee, S. H., & Lazzara, M. J. (2021) · Current Opinion in Systems Biology · doi:10.1016/j.coisb.2021.05.010 · Cited by 23 · see citing works
Functional and Clinical Proteomic Exploration of Pancreatic Cancer
Huang, P., Gao, W., Fu, C., & Tian, R. (2023) · Molecular & Cellular Proteomics · doi:10.1016/j.mcpro.2023.100575 · Cited by 23 · see citing works
“Another study generated global proteomic and phosphoproteomic datasets of tissues from PDAC mouse models to identify Kras-driven signaling networks (30).”
BackgroundOmics-based molecular classifications empowering in precision oncology
Zhou, Z., Lin, T., Chen, S., Zhang, G., Xu, Y., Zou, H., Zhou, A., Zhang, Y., Weng, S., Han, X., et al. (2024) · Cellular Oncology · doi:10.1007/s13402-023-00912-8 · Cited by 22 · see citing works
“The pertinence of phosphoproteomic and proteomic profiling in comprehending tumor heterogeneity has been demonstrated [124, 125].”
Multiomics Empowers Predictive Pancreatic Cancer Immunotherapy
Montagne, J. M., Jaffee, E. M., & Fertig, E. J. (2023) · The Journal of Immunology · doi:10.4049/jimmunol.2200660 · Cited by 18 · see citing works
Oncogenic K-Ras suppresses global miRNA function
Shui, B., Beyett, T. S., Chen, Z., Li, X., Rocca, G. L., Gazlay, W., Eck, M. J., Lau, K. S., Ventura, A., & Haigis, K. M. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.06.008 · Cited by 17 · see citing works
Self-citationBironzo, P., Cani, M., Jacobs, F., Napoli, V. M., Listì, A., Passiglia, F., Righi, L., Maïo, M. D., Novello, S., & Scagliotti, G. V. (2023) · Cancer · doi:10.1002/cncr.34731 · Cited by 14 · see citing works
“8 Recent data on an isogenic system, including the most common NSCLC KRAS ‐ activating mutations, have shed new light on growth patterns as well as sensitivity to targeted agents of specific isoforms.”
Dräger, A., Helikar, T., Barberis, M., Birtwistle, M. R., Calzone, L., Chaouiya, C., Hasenauer, J., Karr, J. R., Niarakis, A., Martínez, M. R., et al. (2021) · Bioinformatics · doi:10.1093/bioinformatics/btab229 · Cited by 14 · see citing works
Suárez-López, L., Shui, B., Brubaker, D. K., Hill, M., Bergendorf, A. M., Changelian, P. S., Laguna, A., Starchenko, A., Lauffenburger, D. A., & Haigis, K. M. (2021) · iScience · doi:10.1016/j.isci.2021.103406 · Cited by 13 · see citing works
Self-citationKinase activities in pancreatic ductal adenocarcinoma with prognostic and therapeutic avenues
Vallés‐Martí, A., Haas, R. R. D. G., Henneman, A. A., Piersma, S. R., Pham, T. V., Knol, J. C., Verheij, J., Dijk, F., Halfwerk, H., Giovannetti, E., et al. (2024) · Molecular Oncology · doi:10.1002/1878-0261.13625 · Cited by 11 · see citing works
STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer
D’Amico, S., Kirillov, V., Petrenko, O., & Reich, N. C. (2024) · eLife · doi:10.7554/elife.92559.2 · Cited by 10 · see citing works
Stuart, S., Watchorn, J., & Gu, F. (2023) · Digital Discovery · doi:10.1039/d3dd00009e · Cited by 9 · see citing works
Carroll, M. J., García‐Reyero, N., Perkins, E. J., & Lauffenburger, D. A. (2021) · Integrative Biology · doi:10.1093/intbio/zyab016 · Cited by 8 · see citing works
Self-citationHang, J., Ouyang, H., Wei, F., Zhong, Q., Yuan, W., Jiang, L., & Liu, Z. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.941046 · Cited by 7 · see citing works
“Kinase-pathway network analysis (KiPNA) We used a network analysis framework that is developed for relating kinase signaling with pathway dysregulation (37).”
MethodAutoTransOP: translating omics signatures without orthologue requirements using deep learning
Meimetis, N., Pullen, K. M., Zhu, D. Y., Nilsson, A., Hoang, T. N., Magliacane, S., & Lauffenburger, D. A. (2024) · npj Systems Biology and Applications · doi:10.1038/s41540-024-00341-9 · Cited by 6 · see citing works
Self-citationOncogenic dependency plays a dominant role in the immune response to cancer
Li, J., D’Amico, S., Kirillov, V., Petrenko, O., & Reich, N. C. (2023) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2308635120 · Cited by 6 · see citing works
“Tumor types that did not form distinct clusters (H2 hybrids) showed elevated scores for the cell cycle and DNA replication (E2F targets, G2/M checkpoint, and MYC targets), supporting published results from mice (25) ( SI Appendix , Fig.”
ResultComputational translation of mouse models of osteoarthritis predicts human disease
Frost, M., Ball, B. K., Pendyala, M., Douglas, S. R., Brubaker, D. K., & Chan, D. D. (2025) · Osteoarthritis and Cartilage · doi:10.1016/j.joca.2025.09.010 · Cited by 5 · see citing works
Self-citationTRIP13 protects pancreatic cancer cells against intrinsic and therapy-induced DNA replication stress
Anand, J. R., Droby, G. N., Joseph, S., Patel, U., Zhang, X., Klomp, J. A., Der, C. J., Purvis, J. E., Wolff, S. C., Bowser, J. L., et al. (2025) · NAR Cancer · doi:10.1093/narcan/zcaf009 · Cited by 5 · see citing works
Mutant KRAS-Associated Proteome Is Mainly Controlled by Exogenous Factors
Carvalho, P. D., Martins, F., Carvalho, J., Oliveira, M. J., & Velho, S. (2022) · Cells · doi:10.3390/cells11131988 · Cited by 5 · see citing works
“dependent, showing allele and tissue/tumor specificities [8,9].”
Fighting the Sixth Decade of the Cancer War with Better Cancer Models
Tuveson, D. A. (2021) · Cancer Discovery · doi:10.1158/2159-8290.cd-21-0234 · Cited by 5 · see citing works
Future Directions for Quantitative Systems Pharmacology
Schoeberl, B., Musante, C. J., & Ramanujan, S. (2024) · Handbook of experimental pharmacology · doi:10.1007/164_2024_737 · Cited by 5 · see citing works
Direct genetic transformation bypasses tumor-associated DNA methylation alterations
Hetzel, S., Hodis, E., Triglia, E. T., Kovacsovics, A., Steinmann, K. E., Gnirke, A., Cui, M., McQuaid, D. C., Weigert, R., Pohl, G., et al. (2025) · Genome biology · doi:10.1186/s13059-025-03650-2 · Cited by 3 · see citing works
“…colon adenoma/carcinoma models ( Apc Min/ + and Apc fl/ + combined with different Kras mutations ( Kras G12D/ + , Kras G13D/ + or Kras A146T/ + )) [40–42] as well as target enrichment methylation data sets for a pancreatic adenocarcinoma model (driven by Kras G12D/ + ) that can be further…”
Rajarathinam, B., Nandan, D., Venugopal, P., Nair, A. M., John, S., Nair, B. G., & Aradhya, R. (2026) · International Journal of Molecular Sciences · doi:10.3390/ijms27072989 · Cited by 3 · see citing works
Zhang, G., Chen, Y., Yan, C., Wang, J., Liang, W., Luo, J., & Luo, H. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1398231 · Cited by 3 · see citing works
Pullen, K. M., Finethy, R., Ko, S.-H. B., Reames, C. J., Sassetti, C. M., & Lauffenburger, D. A. (2025) · npj Systems Biology and Applications · doi:10.1038/s41540-024-00487-6 · Cited by 4 · see citing works
Self-citationSTAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancer
D’Amico, S., Kirillov, V., Petrenko, O., & Reich, N. C. (2024) · eLife · doi:10.7554/elife.92559 · Cited by 3 · see citing works
KRAS regulation of miRNA: Stepping on the brake to go faster
Stalnecker, C. A., & Der, C. J. (2023) · Molecular Cell · doi:10.1016/j.molcel.2023.06.029 · Cited by 2 · see citing works
STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancerPreprint
D’Amico, S., Kirillov, V., Petrenko, O., & Reich, N. C. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.09.01.555946 · Cited by 2 · see citing works
“It integrates KRAS signaling outputs, with effector topologies, cooperating mutations, and environmental cues (23, 25, 26, 47).”
BackgroundThe impact of K-Ras Gly12 mutants on homeostasis and tumorigenesis in the colonic epithelium
Yang, M. H., Sheth, S., Shui, B., Grabski, I. N., Park, S. S., Galán‐Cobo, A., Irizarri, R., Heymach, J. V., Dow, L. E., & Haigis, K. M. (2026) · Oncogene · doi:10.1038/s41388-026-03771-3 · Cited by 1 · see citing works
Self-citationAllosteric regulation of switch-II controls K-Ras oncogenicityPreprint
Yang, M. H., Tran, T. H., Hunt, B., Agnor, R., Johnson, C. W., Waybright, T. J., Nowak, J. A., Stephen, A. G., Simanshu, D. K., & Haigis, K. M. (2022) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2022.09.20.508702 · Cited by 1 · see citing works
“Although there are many available small molecule inhibitors that target kinases downstream of K-Ras, effector-based therapy is complicated by the highly context-dependent nature of K-Ras signaling [18, 29].”
BackgroundSelf-citationTranslational Models for ENDP Assessment
Martin, F. P., Titz, B., Frentzel, S., Schlage, W. K., Ivanov, N. V., Hoeng, J., & Peitsch, M. C. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820490-0.00010-9
Kinase Activities in Pancreatic Ductal Adenocarcinoma with Prognostic and Therapeutic AvenuesPreprint
Vallés‐Martí, A., de Haas, R. R. D. G., Henneman, A. A., Piersma, S. R., Pham, T. V., Knol, J. C., Verheij, J., Dijk, F., Halfwerk, H., Giovannetti, E., et al. (2023) · SSRN Electronic Journal · doi:10.2139/ssrn.4506560
STAT3 is a genetic modifier of TGF-beta induced EMT in KRAS mutant pancreatic cancerPreprint
D’Amico, S., Kirillov, V., Petrenko, O., & Reich, N. C. (2024) · eLife · doi:10.7554/elife.92559.1
D’Amico, S., Kirillov, V., Petrenko, O., & Reich, N. C. (2024) · eLife · doi:10.7554/elife.92559.1.sa3
TRIP13 protects pancreatic cancer cells against intrinsic and therapy-induced DNA replication stressPreprint
Anand, J. R., Droby, G. N., Joseph, S., Patel, U., Zhang, X., Klomp, J. A., Der, C. J., Purvis, J. E., Wolff, S. C., Bowser, J. L., et al. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.01.26.634889
Why are Some Tissues More Vulnerable? Revisiting Tissue Specificity in Hereditary Cancer Syndromes
Kozak, V. N., de Oliveira, J. C., Gradia, D. F., Mathias, C., & Ribeiro, E. M. S. F. (2026) · Molecular Diagnosis & Therapy · doi:10.1007/s40291-026-00845-6
“Co-mutated partners in each organ revealed organ-and allele-specific dependencies, leading to distinct resultant cellular phenotypes, which has also been observed in other studies [83, 84].”
- Authors
- Brubaker, D. K., Paulo, J. A., Sheth, S., Poulin, E. J., Popow, O., Joughin, B. A., Strasser, S. D., Starchenko, A., Gygi, S. P., Lauffenburger, D. A., & Haigis, K. M.
- Affiliations
- Beth Israel Deaconess Medical Center (US)
- Massachusetts Institute of Technology (US)
- Harvard University (US)
- Corresponding author
- Lauffenburger, Douglas A.
- Haigis, Kevin M.
- ORCID
- Venue
- Cell Systems
- Publisher
- Elsevier BV
- Published
- 2019-09
- Volume
- 9
- Issue
- 3
- Pages
- 258-270.e6
- ISSN
- 2405-4712 (ISSN-L)
- PMC
- PMC6816257
- OpenAlex
- W2972639591
- Cited by
- 57
- References
- 56
- Citations by year
- 2026: 3 · 2025: 5 · 2024: 11 · 2023: 10 · 2022: 9 · 2021: 12 · 2020: 6 · 2019: 1
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell Systems (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc-nd)
- Funders
- National Cancer Institute
- National Institute of Diabetes and Digestive and Kidney Diseases
- 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 › Bioinformatics and Genomic Networks
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Tyrosine Phosphatases
- Keywords
- KRAS signaling, KRAS mutation, colorectal cancer, pancreatic ductal adenocarcinoma, proteogenomics, phosphoproteomics, synthetic lethality, therapeutic target
- MeSH terms
- Proteogenomics, Animals, Disease Models, Animal, Humans, Mutation, Protein Biosynthesis, Colorectal Neoplasms, Signal Transduction, Proto-Oncogene Proteins p21(ras), Computational Biology, Carcinoma, Pancreatic Ductal, Mice, Gene Regulatory Networks, Metabolic Networks and Pathways, Tumor Microenvironment, Cellular Microenvironment, Carcinogenesis, Datasets as Topic
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