Oncogenic KRAS Regulates Tumor Cell Signaling via Stromal Reciprocation
Open accessAbstract
Oncogenic mutations regulate signaling within both tumor cells and adjacent stromal cells. Here, we show that oncogenic KRAS (KRAS(G12D)) also regulates tumor cell signaling via stromal cells. By combining cell-specific proteome labeling with multivariate phosphoproteomics, we analyzed heterocellular KRAS(G12D) signaling in pancreatic ductal adenocarcinoma (PDA) cells. Tumor cell KRAS(G12D) engages heterotypic fibroblasts, which subsequently instigate reciprocal signaling in the tumor cells. Reciprocal signaling employs additional kinases and doubles the number of regulated signaling nodes from cell-autonomous KRAS(G12D). Consequently, reciprocal KRAS(G12D) produces a tumor cell phosphoproteome and total proteome that is distinct from cell-autonomous KRAS(G12D) alone. Reciprocal signaling regulates tumor cell proliferation and apoptosis and increases mitochondrial capacity via an IGF1R/AXL-AKT axis. These results demonstrate that oncogene signaling should be viewed as a heterocellular process and that our existing cell-autonomous perspective underrepresents the extent of oncogene signaling in cancer. VIDEO ABSTRACT.
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?
Production of TGFβ, LIF, GAS6, FGF5, GDF15 and HGF promotes invasive and proliferative behaviour in cancer cells.
“The production of TGFβ, leukaemia inhibitory factor (LIF), growth arrest-specific protein 6 (GAS6), fibroblast growth factor 5 (FGF5), growth differentiation factor 15 (GDF15) and hepatocyte growth factor (HGF) promotes invasive and proliferative behaviour in cancer cells52,109–112.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [111]
The Results sections on stromal signaling and tumor-cell phenotypes report that activated pancreatic stromal cells secrete GAS6 and that reciprocal signaling through IGF1R/AXL–AKT increases tumor-cell proliferation. The cited paper does not establish that the full list of six factors promotes these behaviours, nor does it report an invasive-behaviour result for them. Page numbers are not available in our copy. (LLM, conf=0.88)
Experimental — accuracy not yet measuredKRAS mutation or different p53 mutational status can influence CAFs in PDAC.
“Work in PDAC has shown how KRAS mutation or different p53 mutational status can influence CAFs111,136.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [111]
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
Feig, C., Jones, J. O., Kraman, M., Wells, R. J. B., Deonarine, A., Chan, D. S., Connell, C. M., Roberts, E. W., Zhao, Q., Caballero, O. L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320318110 · Cited by 2,100 · see citing works
Oncogenic Kras maintains pancreatic tumors through regulation of anabolic glucose metabolism
Ying, H., Kimmelman, A. C., Lyssiotis, C. A., Hua, S., Chu, G. C., Fletcher-Sananikone, E., Locasale, J. W., Son, J., Zhang, H., Coloff, J. L., et al. (2012) · Cell · doi:10.1016/j.cell.2012.01.058 · Cited by 2,043 · see citing works
Oncogene ablation-resistant pancreatic cancer cells depend on mitochondrial function
Viale, A., Pettazzoni, P., Lyssiotis, C. A., Ying, H., Sánchez, N., Marchesini, M., Carugo, A., Green, T., Seth, S., Giuliani, V., et al. (2014) · Nature · doi:10.1038/nature13611 · Cited by 1,259 · see citing works
Oncogenic Kras is required for both the initiation and maintenance of pancreatic cancer in mice
Collins, M. A., Bednar, F., Zhang, Y., Brisset, J.-C., Galbán, S., Galbán, C. J., Rakshit, S., Flannagan, K. S., Adsay, N. V., & Pasca di Magliano, M. (2012) · Journal of Clinical Investigation · doi:10.1172/jci59227 · Cited by 770 · see citing works
Flagged first, then by citations
Research works printed but not linked: 40
- Almoguera C. Shibata D. Forrester K. Martin J. Arnheim N. Perucho M. Most human carcinomas of the exocrine pancreas contain mutant c-K-ras genes Cell 53 1988 549 554 2453289
- Baer R. Cintas C. Dufresne M. Cassant-Sourdy S. Schönhuber N. Planque L. Lulka H. Couderc B. Bousquet C. Garmy-Susini B. Pancreatic cell plasticity and cancer initiation induced by oncogenic Kras is completely dependent on wild-type PI 3-kinase p110α Genes Dev. 28 2014 2621 2635 25452273 PMC4248293
- Brock A. Krause S. Ingber D.E. Control of cancer formation by intrinsic genetic noise and microenvironmental cues Nat. Rev. Cancer 15 2015 499 509 26156637
- Croce C.M. Oncogenes and cancer N. Engl. J. Med. 358 2008 502 511 18234754
- Egeblad M. Nakasone E.S. Werb Z. Tumors as organs: complex tissues that interface with the entire organism Dev. Cell 18 2010 884 901 20627072 PMC2905377
- Eser S. Reiff N. Messer M. Seidler B. Gottschalk K. Dobler M. Hieber M. Arbeiter A. Klein S. Kong B. Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer Cancer Cell 23 2013 406 420 23453624
- Eser S. Schnieke A. Schneider G. Saur D. Oncogenic KRAS signalling in pancreatic cancer Br. J. Cancer 111 2014 817 822 24755884 PMC4150259
- Fendrich V. Oh E. Bang S. Karikari C. Ottenhof N. Bisht S. Lauth M. Brossart P. Katsanis N. Maitra A. Feldmann G. Ectopic overexpression of Sonic Hedgehog (Shh) induces stromal expansion and metaplasia in the adult murine pancreas Neoplasia 13 2011 923 930 22028618 PMC3201569
- Friedl P. Alexander S. Cancer invasion and the microenvironment: plasticity and reciprocity Cell 147 2011 992 1009 22118458
- Gauthier N.P. Soufi B. Walkowicz W.E. Pedicord V.A. Mavrakis K.J. Macek B. Gin D.Y. Sander C. Miller M.L. Cell-selective labeling using amino acid precursors for proteomic studies of multicellular environments Nat. Methods 10 2013 768 773 23817070 PMC4002004
- Ghesquière B. Wong B.W. Kuchnio A. Carmeliet P. Metabolism of stromal and immune cells in health and disease Nature 511 2014 167 176 25008522
- Hanahan D. Weinberg R.A. Hallmarks of cancer: the next generation Cell 144 2011 646 674 21376230
- Janes K.A. Kelly J.R. Gaudet S. Albeck J.G. Sorger P.K. Lauffenburger D.A. Cue-signal-response analysis of TNF-induced apoptosis by partial least squares regression of dynamic multivariate data J. Comput. Biol. 11 2004 544 561 15579231
- Janes K.A. Albeck J.G. Gaudet S. Sorger P.K. Lauffenburger D.A. Yaffe M.B. A systems model of signaling identifies a molecular basis set for cytokine-induced apoptosis Science 310 2005 1646 1653 16339439
- Jorgensen C. Sherman A. Chen G.I. Pasculescu A. Poliakov A. Hsiung M. Larsen B. Wilkinson D.G. Linding R. Pawson T. Cell-specific information processing in segregating populations of Eph receptor ephrin-expressing cells Science 326 2009 1502 1509 20007894
- Kolch W. Halasz M. Granovskaya M. Kholodenko B.N. The dynamic control of signal transduction networks in cancer cells Nat. Rev. Cancer 15 2015 515 527 26289315
- Kraman M. Bambrough P.J. Arnold J.N. Roberts E.W. Magiera L. Jones J.O. Gopinathan A. Tuveson D.A. Fearon D.T. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha Science 330 2010 827 830 21051638
- Lauth M. Bergström A. Shimokawa T. Tostar U. Jin Q. Fendrich V. Guerra C. Barbacid M. Toftgård R. DYRK1B-dependent autocrine-to-paracrine shift of Hedgehog signaling by mutant RAS Nat. Struct. Mol. Biol. 17 2010 718 725 20512148
- Lee J.J. Perera R.M. Wang H. Wu D.C. Liu X.S. Han S. Fitamant J. Jones P.D. Ghanta K.S. Kawano S. Stromal response to Hedgehog signaling restrains pancreatic cancer progression Proc. Natl. Acad. Sci. USA 111 2014 E3091 E3100 25024225 PMC4121834
- McAlister G.C. Huttlin E.L. Haas W. Ting L. Jedrychowski M.P. Rogers J.C. Kuhn K. Pike I. Grothe R.A. Blethrow J.D. Gygi S.P. Increasing the multiplexing capacity of TMTs using reporter ion isotopologues with isobaric masses Anal. Chem. 84 2012 7469 7478 22880955 PMC3715028
- McDowell G.S. Gaun A. Steen H. iFASP: combining isobaric mass tagging with filter-aided sample preparation J. Proteome Res. 12 2013 3809 3812 23692318 PMC4416645
- McNulty D.E. Annan R.S. Hydrophilic interaction chromatography reduces the complexity of the phosphoproteome and improves global phosphopeptide isolation and detection Mol. Cell. Proteomics 7 2008 971 980 18212344
- Miller-Jensen K. Janes K.A. Brugge J.S. Lauffenburger D.A. Common effector processing mediates cell-specific responses to stimuli Nature 448 2007 604 608 17637676
- Neesse A. Michl P. Frese K.K. Feig C. Cook N. Jacobetz M.A. Lolkema M.P. Buchholz M. Olive K.P. Gress T.M. Tuveson D.A. Stromal biology and therapy in pancreatic cancer Gut 60 2011 861 868 20966025
- Olive K.P. Jacobetz M.A. Davidson C.J. Gopinathan A. McIntyre D. Honess D. Madhu B. Goldgraben M.A. Caldwell M.E. Allard D. Inhibition of Hedgehog signaling enhances delivery of chemotherapy in a mouse model of pancreatic cancer Science 324 2009 1457 1461 19460966 PMC2998180
- Ong S.E. Blagoev B. Kratchmarova I. Kristensen D.B. Steen H. Pandey A. Mann M. Stable isotope labeling by amino acids in cell culture, SILAC, as a simple and accurate approach to expression proteomics Mol. Cell. Proteomics 1 2002 376 386 12118079
- Pylayeva-Gupta Y. Grabocka E. Bar-Sagi D. RAS oncogenes: weaving a tumorigenic web Nat. Rev. Cancer 11 2011 761 774 21993244 PMC3632399
- Quail D.F. Joyce J.A. Microenvironmental regulation of tumor progression and metastasis Nat. Med. 19 2013 1423 1437 24202395 PMC3954707
- Rhim A.D. Oberstein P.E. Thomas D.H. Mirek E.T. Palermo C.F. Sastra S.A. Dekleva E.N. Saunders T. Becerra C.P. Tattersall I.W. Stromal elements act to restrain, rather than support, pancreatic ductal adenocarcinoma Cancer Cell 25 2014 735 747 24856585 PMC4096698
- Sherman M.H. Yu R.T. Engle D.D. Ding N. Atkins A.R. Tiriac H. Collisson E.A. Connor F. Van Dyke T. Kozlov S. Vitamin D receptor-mediated stromal reprogramming suppresses pancreatitis and enhances pancreatic cancer therapy Cell 159 2014 80 93 25259922 PMC4177038
- Simmons A.J. Banerjee A. McKinley E.T. Scurrah C.R. Herring C.A. Gewin L.S. Masuzaki R. Karp S.J. Franklin J.L. Gerdes M.J. Cytometry-based single-cell analysis of intact epithelial signaling reveals MAPK activation divergent from TNF-α-induced apoptosis in vivo Mol. Syst. Biol. 11 2015 835 26519361 PMC4631206
- Tape C.J. Norrie I.C. Worboys J.D. Lim L. Lauffenburger D.A. Jørgensen C. Cell-specific labeling enzymes for analysis of cell-cell communication in continuous co-culture Mol. Cell. Proteomics 13 2014 1866 1876 24820872 PMC4083121
- Tape C.J. Worboys J.D. Sinclair J. Gourlay R. Vogt J. McMahon K.M. Trost M. Lauffenburger D.A. Lamont D.J. Jørgensen C. Reproducible automated phosphopeptide enrichment using magnetic TiO2 and Ti-IMAC Anal. Chem. 86 2014 10296 10302 25233145 PMC4206527
- Thayer S.P. di Magliano M.P. Heiser P.W. Nielsen C.M. Roberts D.J. Lauwers G.Y. Qi Y.P. Gysin S. Fernández-del Castillo C. Yajnik V. Hedgehog is an early and late mediator of pancreatic cancer tumorigenesis Nature 425 2003 851 856 14520413 PMC3688051
- Thompson A. Schäfer J. Kuhn K. Kienle S. Schwarz J. Schmidt G. Neumann T. Johnstone R. Mohammed A.K. Hamon C. Tandem mass tags: a novel quantification strategy for comparative analysis of complex protein mixtures by MS/MS Anal. Chem. 75 2003 1895 1904 12713048
- Tian H. Callahan C.A. DuPree K.J. Darbonne W.C. Ahn C.P. Scales S.J. de Sauvage F.J. Hedgehog signaling is restricted to the stromal compartment during pancreatic carcinogenesis Proc. Natl. Acad. Sci. USA 106 2009 4254 4259 19246386 PMC2647977
- Vizcaíno J.A. Côté R.G. Csordas A. Dianes J.A. Fabregat A. Foster J.M. Griss J. Alpi E. Birim M. Contell J. The PRoteomics IDEntifications (PRIDE) database and associated tools: status in 2013 Nucleic Acids Res. 41 2013 D1063 D1069 23203882 PMC3531176
- Wiśniewski J.R. Zougman A. Nagaraj N. Mann M. Universal sample preparation method for proteome analysis Nat. Methods 6 2009 359 362 19377485
- Wu C.Y. Carpenter E.S. Takeuchi K.K. Halbrook C.J. Peverley L.V. Bien H. Hall J.C. DelGiorno K.E. Pal D. Song Y. PI3K regulation of RAC1 is required for KRAS-induced pancreatic tumorigenesis in mice Gastroenterology 147 2014 1405 1416 25311989 PMC4252806
- Yauch R.L. Gould S.E. Scales S.J. Tang T. Tian H. Ahn C.P. Marshall D. Fu L. Januario T. Kallop D. A paracrine requirement for hedgehog signalling in cancer Nature 455 2008 406 410 18754008
Cited by
Sorted by citations
A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863 · see citing works
Self-citationDiversity and biology of cancer-associated fibroblasts
Biffi, G., & Tuveson, D. A. (2021) · Physiological Reviews · doi:10.1152/physrev.00048.2019 · Cited by 1,265 · see citing works
Clinical and therapeutic relevance of cancer-associated fibroblasts
Chen, Y., McAndrews, K. M., & Kalluri, R. (2021) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-021-00546-5 · Cited by 1,230 · see citing works
Pancreatic stellate cells support tumour metabolism through autophagic alanine secretion
Sousa, C. M., Biancur, D. E., Wang, X., Halbrook, C. J., Sherman, M. H., Zhang, L., Kremer, D., Hwang, R. F., Witkiewicz, A. K., Ying, H., et al. (2016) · Nature · doi:10.1038/nature19084 · Cited by 1,122 · see citing works
Pancreatic cancer stroma: an update on therapeutic targeting strategies
Hosein, A. N., Brekken, R. A., & Maitra, A. (2020) · Nature Reviews Gastroenterology & Hepatology · doi:10.1038/s41575-020-0300-1 · Cited by 950 · see citing works
Wang, S., Zheng, Y., Yang, F., Zhu, L., Zhu, X.-Q., Wang, Z.-F., Wu, X.-L., Zhou, C.-H., Yan, J.-Y., Hu, B.-Y., et al. (2021) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-021-00659-4 · Cited by 369 · see citing works
Pan-cancer deconvolution of tumour composition using DNA methylation
Chakravarthy, A., Furness, A., Joshi, K., Ghorani, E., Ford, K., Ward, M. J., King, E. V., Lechner, M., Marafioti, T., Quezada, S. A., et al. (2018) · Nature Communications · doi:10.1038/s41467-018-05570-1 · Cited by 327 · see citing works
Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity
Hutton, C., Heider, F., Blanco-Gomez, A., Banyard, A., Kononov, A., Zhang, X., Karim, S., Paulus-Hock, V., Watt, D., Steele, N., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.06.017 · Cited by 337 · see citing works
Self-citationA Stromal Lysolipid–Autotaxin Signaling Axis Promotes Pancreatic Tumor Progression
Auciello, F. R., Bulusu, V., Oon, C., Tait-Mulder, J., Berry, M., Bhattacharyya, S., Tumanov, S., Allen-Petersen, B. L., Link, J., Kendsersky, N. D., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-1212 · Cited by 332 · see citing works
Acetyl-CoA Metabolism Supports Multistep Pancreatic Tumorigenesis
Carrer, A., Trefely, S., Zhao, S., Campbell, S. L., Norgard, R. J., Schultz, K. C., Sidoli, S., Parris, J. L. D., Affronti, H. C., Sivanand, S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0567 · Cited by 313 · see citing works
Candido, J. B., Morton, J. P., Bailey, P., Campbell, A. D., Karim, S. A., Jamieson, T., Lapienyte, L., Gopinathan, A., Clark, W., McGhee, E. J., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.03.131 · Cited by 224 · see citing works
KRAS Oncogenic Signaling Extends beyond Cancer Cells to Orchestrate the Microenvironment
Dias Carvalho, P., Guimarães, C. F., Cardoso, A. P., Mendonça, S., Costa, Â. M., Oliveira, M. J., & Velho, S. (2018) · Cancer Research · doi:10.1158/0008-5472.can-17-2084 · Cited by 202 · see citing works
KRAS <sup>G12C</sup> inhibition produces a driver-limited state revealing collateral dependencies
Lou, K., Steri, V., Ge, A. Y., Hwang, Y. C., Yogodzinski, C. H., Shkedi, A. R., Choi, A. L. M., Mitchell, D. C., Swaney, D. L., Hann, B., et al. (2019) · Science Signaling · doi:10.1126/scisignal.aaw9450 · Cited by 175 · see citing works
Deoxycytidine release from pancreatic stellate cells promotes gemcitabine resistance
Dalin, S., Sullivan, M. R., Lau, A. N., Grauman-Boss, B., Mueller, H. S., Kreidl, E., Fenoglio, S., Luengo, A., Lees, J. A., Vander Heiden, M. G., et al. (2019) · Cancer Research · doi:10.1158/0008-5472.can-19-0960 · Cited by 156 · see citing works
Self-citationHu, H.-F., Ye, Z., Qin, Y., Xu, X.-W., Yu, X.-J., Zhuo, Q.-F., & Ji, S.-R. (2021) · Acta Pharmacologica Sinica · doi:10.1038/s41401-020-00584-2 · Cited by 149 · see citing works
Hu, C.-M., Tien, S.-C., Hsieh, P.-K., Jeng, Y.-M., Chang, M.-C., Chang, Y.-T., Chen, Y.-J., Chen, Y.-J., Lee, E. Y.-H. P., & Lee, W.-H. (2019) · Cell Metabolism · doi:10.1016/j.cmet.2019.02.005 · Cited by 123 · see citing works
Metabolic requirement for GOT2 in pancreatic cancer depends on environmental context
Kerk, S. A., Lin, L., Myers, A. L., Sutton, D. J., Andren, A., Sajjakulnukit, P., Zhang, L., Zhang, Y., Jiménez, J. A., Nelson, B. S., et al. (2022) · eLife · doi:10.7554/elife.73245 · Cited by 108 · see citing works
Oncogenic KRAS Drives Lipofibrogenesis to Promote Angiogenesis and Colon Cancer Progression
Hsu, W.-H., LaBella, K. A., Lin, Y., Xu, P., Lee, R., Hsieh, C.-E., Yang, L., Zhou, A., Blecher, J. M., Wu, C.-J., et al. (2023) · Cancer Discovery · doi:10.1158/2159-8290.cd-22-1467 · Cited by 125 · see citing works
Epithelial and stromal co-evolution and complicity in pancreatic cancer
Hingorani, S. R. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00530-w · Cited by 108 · see citing works
Franco-Barraza, J., Francescone, R., Luong, T., Shah, N., Madhani, R., Cukierman, G., Dulaimi, E., Devarajan, K., Egleston, B. L., Nicolas, E., et al. (2017) · eLife · doi:10.7554/elife.20600 · Cited by 112 · see citing works
Santana-Codina, N., Chandhoke, A. S., Yu, Q., Małachowska, B., Kuljanin, M., Gikandi, A., Stańczak, M., Gableske, S., Jedrychowski, M. P., Scott, D. A., et al. (2020) · Cell Reports · doi:10.1016/j.celrep.2020.03.021 · Cited by 77 · see citing works
Malik, R., Luong, T., Cao, X., Han, B., Shah, N., Franco-Barraza, J., Han, L., Shenoy, V. B., Lelkes, P. I., & Cukierman, E. (2019) · Matrix Biology · doi:10.1016/j.matbio.2018.11.001 · Cited by 74 · see citing works
Boyer, S., Lee, H.-J., Steele, N., Zhang, L., Sajjakulnukit, P., Andren, A., Ward, M. H., Singh, R., Basrur, V., Zhang, Y., et al. (2022) · eLife · doi:10.7554/elife.73796 · Cited by 56 · see citing works
Brunel, A., Samain, R., Neuzillet, C., & Bousquet, C. (2018) · Translational Cancer Research · doi:10.21037/tcr.2018.06.09 · Cited by 5 · see citing works
- Authors
- Tape, C. J., Ling, S., Dimitriadi, M., McMahon, K. M., Worboys, J. D., Leong, H. S., Norrie, I. C., Miller, C. J., Poulogiannis, G., Lauffenburger, D. A., & Jørgensen, C.
- Affiliations
- Institute of Cancer Research (GB)
- University of Manchester (GB)
- Massachusetts Institute of Technology (US)
- Corresponding author
- Jørgensen, Claus
- ORCID
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2016-05
- Volume
- 165
- Issue
- 4
- Pages
- 910-920
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC4868820
- OpenAlex
- W2341205093
- Cited by
- 369
- References
- 4
- Citations by year
- 2026: 20 · 2025: 21 · 2024: 31 · 2023: 29 · 2022: 48 · 2021: 48 · 2020: 47 · 2019: 31 · 2018: 41 · 2017: 38 · 2016: 15
- FWCI
- 21.66
- Type
- journal article
- Language
- en
- Update notices
- erratum (2016-06-16)
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Cell (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Explorer (The University of Manchester) (publishedVersion, cc-by)
- ENLIGHTEN (Jurnal Bimbingan dan Konseling Islam) (acceptedVersion)
- University of Hertfordshire Research Archive (University of Hertfordshire) (acceptedVersion)
- University of Hertfordshire Research Archive (University of Hertfordshire) (submittedVersion, cc-by)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- UCL Discovery (University College London) (submittedVersion)
- Funders
- Cancer Research Institute
- Wellcome Trust
- Cancer Research UK (12905, 19258, A19258, 15675)
- Rosetrees Trust
- National Institutes of Health (CA112967)
- National Cancer Institute (U54CA112967, R01CA096504, P30CA014051)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Health Sciences › Medicine › Oncology › Pancreatic and Hepatic Oncology Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- oncogenic KRAS, KRAS G12D, tumor stroma, pancreatic ductal adenocarcinoma, cancer-associated fibroblasts, phosphoproteomics, IGF-1 receptor, AXL, Akt signaling, mitochondrial function, cell proliferation, apoptosis
- MeSH terms
- Animals, Cell Communication, Humans, Pancreatic Neoplasms, Phosphoproteins, Signal Transduction, Proto-Oncogene Proteins p21(ras), Stromal Cells, Proteome, Carcinoma, Pancreatic Ductal, Mice
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
