دورية أكاديمية
Non-cell-autonomous cancer progression from chromosomal instability.
العنوان: | Non-cell-autonomous cancer progression from chromosomal instability. |
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المؤلفون: | Li J; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hubisz MJ; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA.; Bioinformatics Facility, Institute of Biotechnology, Cornell University, Ithaca, NY, USA., Earlie EM; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA., Duran MA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Hong C; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Varela AA; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA., Lettera E; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Deyell M; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA., Tavora B; Volastra Therapeutics Inc., New York, NY, USA., Havel JJ; Volastra Therapeutics Inc., New York, NY, USA., Phyu SM; Department of Oncology, Medical Sciences Division, University of Oxford, Oxford, UK., Amin AD; Columbia Center for Translational Immunology, New York, NY, USA.; Division of Hematology and Oncology, Columbia University Medical Center, New York, NY, USA., Budre K; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA., Kamiya E; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA., Cavallo JA; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Garris C; Department of Pathology, Harvard Medical School, Boston, MA, USA.; Center for Systems Biology, Massachusetts General Hospital, Boston, MA, USA., Powell S; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Reis-Filho JS; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Wen H; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Bettigole S; Volastra Therapeutics Inc., New York, NY, USA., Khan AJ; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA., Izar B; Columbia Center for Translational Immunology, New York, NY, USA.; Division of Hematology and Oncology, Columbia University Medical Center, New York, NY, USA., Parkes EE; Department of Oncology, Medical Sciences Division, University of Oxford, Oxford, UK., Laughney AM; Department of Physiology, Biophysics, and Systems Biology, Weill Cornell Medicine, New York, NY, USA. ashley.laughney@gmail.com.; Meyer Cancer Center, Weill Cornell Medicine, New York, NY, USA. ashley.laughney@gmail.com.; Institute for Computational Biomedicine, Weill Cornell Medicine, New York, NY, USA. ashley.laughney@gmail.com., Bakhoum SF; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. samuel.bakhoum@gmail.com.; Department of Radiation Oncology, Memorial Sloan Kettering Cancer Center, New York, NY, USA. samuel.bakhoum@gmail.com. |
المصدر: | Nature [Nature] 2023 Aug; Vol. 620 (7976), pp. 1080-1088. Date of Electronic Publication: 2023 Aug 23. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Nature Publishing Group Country of Publication: England NLM ID: 0410462 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1476-4687 (Electronic) Linking ISSN: 00280836 NLM ISO Abbreviation: Nature Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Basingstoke : Nature Publishing Group Original Publication: London, Macmillan Journals ltd. |
مواضيع طبية MeSH: | Chromosomal Instability* , Disease Progression* , Neoplasms*/genetics , Neoplasms*/immunology , Neoplasms*/pathology, Humans ; Benchmarking ; Cell Communication ; Colorectal Neoplasms/drug therapy ; Colorectal Neoplasms/genetics ; Colorectal Neoplasms/immunology ; Colorectal Neoplasms/pathology ; Melanoma/drug therapy ; Melanoma/genetics ; Melanoma/immunology ; Melanoma/pathology ; Tumor Microenvironment ; Interferon Type I/immunology ; Neoplasm Metastasis ; Endoplasmic Reticulum Stress ; Signal Transduction ; Triple Negative Breast Neoplasms/drug therapy ; Triple Negative Breast Neoplasms/genetics ; Triple Negative Breast Neoplasms/immunology ; Triple Negative Breast Neoplasms/pathology |
مستخلص: | Chromosomal instability (CIN) is a driver of cancer metastasis 1-4 , yet the extent to which this effect depends on the immune system remains unknown. Using ContactTracing-a newly developed, validated and benchmarked tool to infer the nature and conditional dependence of cell-cell interactions from single-cell transcriptomic data-we show that CIN-induced chronic activation of the cGAS-STING pathway promotes downstream signal re-wiring in cancer cells, leading to a pro-metastatic tumour microenvironment. This re-wiring is manifested by type I interferon tachyphylaxis selectively downstream of STING and a corresponding increase in cancer cell-derived endoplasmic reticulum (ER) stress response. Reversal of CIN, depletion of cancer cell STING or inhibition of ER stress response signalling abrogates CIN-dependent effects on the tumour microenvironment and suppresses metastasis in immune competent, but not severely immune compromised, settings. Treatment with STING inhibitors reduces CIN-driven metastasis in melanoma, breast and colorectal cancers in a manner dependent on tumour cell-intrinsic STING. Finally, we show that CIN and pervasive cGAS activation in micronuclei are associated with ER stress signalling, immune suppression and metastasis in human triple-negative breast cancer, highlighting a viable strategy to identify and therapeutically intervene in tumours spurred by CIN-induced inflammation. (© 2023. The Author(s).) |
التعليقات: | Comment in: Cell Res. 2024 Jan;34(1):7-8. doi: 10.1038/s41422-023-00876-2. (PMID: 37739994) Comment in: Mol Biomed. 2024 Jan 23;5(1):4. doi: 10.1186/s43556-023-00166-8. (PMID: 38253764) |
References: | Li, J. et al. Metastasis and immune evasion from extracellular cGAMP hydrolysis. Cancer Discov. 11, 1212–1227 (2021). Bakhoum, S. F. et al. Chromosomal instability drives metastasis through a cytosolic DNA response. Nature 553, 467–472 (2018). Bakhoum, S. F. & Cantley, L. C. The multifaceted role of chromosomal instability in cancer and its microenvironment. Cell 174, 1347–1360 (2018). (PMID: 30193109613642910.1016/j.cell.2018.08.027) Wormann, S. M. et al. APOBEC3A drives deaminase domain-independent chromosomal instability to promote pancreatic cancer metastasis. Nat. Cancer 2, 1338–1356 (2021). (PMID: 3512190210.1038/s43018-021-00268-8) Lengauer, C., Kinzler, K. W. & Vogelstein, B. Genetic instability in colorectal cancers. Nature 386, 623–627 (1997). (PMID: 912158810.1038/386623a0) Lee, A. J. et al. Chromosomal instability confers intrinsic multidrug resistance. Cancer Res. 71, 1858–1870 (2011). (PMID: 21363922305949310.1158/0008-5472.CAN-10-3604) Taylor, A. M. et al. Genomic and functional approaches to understanding cancer aneuploidy. Cancer Cell 33, 676–689 e673 (2018). (PMID: 29622463602819010.1016/j.ccell.2018.03.007) Davoli, T., Uno, H., Wooten, E. C. & Elledge, S. J. Tumor aneuploidy correlates with markers of immune evasion and with reduced response to immunotherapy. Science https://doi.org/10.1126/science.aaf8399 (2017). Bakhoum, S. F. et al. The mitotic origin of chromosomal instability. Curr. Biol. 24, R148–149 (2014). (PMID: 24556433397016410.1016/j.cub.2014.01.019) Thompson, S. L. & Compton, D. A. Examining the link between chromosomal instability and aneuploidy in human cells. J. Cell Biol. 180, 665–672 (2008). (PMID: 18283116226557010.1083/jcb.200712029) Santaguida, S. et al. Chromosome mis-segregation generates cell-cycle-arrested cells with complex karyotypes that are eliminated by the immune system. Dev. Cell 41, 638–651 e635 (2017). (PMID: 28633018553684810.1016/j.devcel.2017.05.022) Laucius, C. D., Orr, B. & Compton, D. A. Chromosomal instability suppresses the growth of K-Ras-induced lung adenomas. Cell Cycle 18, 1702–1713 (2019). (PMID: 31179849664955010.1080/15384101.2019.1629790) Hoevenaar, W. H. M. et al. Degree and site of chromosomal instability define its oncogenic potential. Nat. Commun. 11, 1501 (2020). (PMID: 32198375708389710.1038/s41467-020-15279-9) Nguyen, B. et al. Genomic characterization of metastatic patterns from prospective clinical sequencing of 25,000 patients. Cell 185, 563–575 e511 (2022). (PMID: 35120664914770210.1016/j.cell.2022.01.003) Watkins, T. B. K. et al. Pervasive chromosomal instability and karyotype order in tumour evolution. Nature https://doi.org/10.1038/s41586-020-2698-6 (2020). Bakhoum, S. F., Thompson, S. L., Manning, A. L. & Compton, D. A. Genome stability is ensured by temporal control of kinetochore-microtubule dynamics. Nat. Cell Biol. 11, 27–35 (2009). (PMID: 1906089410.1038/ncb1809) Hatch, E. M., Fischer, A. H., Deerinck, T. J. & Hetzer, M. W. Catastrophic nuclear envelope collapse in cancer cell micronuclei. Cell 154, 47–60 (2013). (PMID: 23827674374977810.1016/j.cell.2013.06.007) Mackenzie, K. J. et al. cGAS surveillance of micronuclei links genome instability to innate immunity. Nature 548, 461–465 (2017). (PMID: 28738408587083010.1038/nature23449) Harding, S. M. et al. Mitotic progression following DNA damage enables pattern recognition within micronuclei. Nature 548, 466–470 (2017). (PMID: 28759889585735710.1038/nature23470) Ablasser, A. & Chen, Z. J. cGAS in action: expanding roles in immunity and inflammation. Science https://doi.org/10.1126/science.aat8657 (2019). Moore, A. T. et al. MCAK associates with the tips of polymerizing microtubules. J. Cell Biol. 169, 391–397 (2005). (PMID: 15883193217194410.1083/jcb.200411089) Liu, H. et al. Nuclear cGAS suppresses DNA repair and promotes tumorigenesis. Nature 563, 131–136 (2018). (PMID: 3035621410.1038/s41586-018-0629-6) Jiang, P. et al. Systematic investigation of cytokine signaling activity at the tissue and single-cell levels. Nat. Methods 18, 1181–1191 (2021). (PMID: 34594031849380910.1038/s41592-021-01274-5) Bartneck, M. et al. The CCR2 + macrophage subset promotes pathogenic angiogenesis for tumor vascularization in fibrotic livers. Cell. Mol. Gastroenterol. Hepatol. 7, 371–390 (2019). (PMID: 3070498510.1016/j.jcmgh.2018.10.007) Wu, S. Z. et al. A single-cell and spatially resolved atlas of human breast cancers. Nat. Genet. 53, 1334–1347 (2021). (PMID: 34493872904482310.1038/s41588-021-00911-1) Dhanda, J. et al. SERPINE1 and SMA expression at the invasive front predict extracapsular spread and survival in oral squamous cell carcinoma. Br. J. Cancer 111, 2114–2121 (2014). (PMID: 25268377426002810.1038/bjc.2014.500) Jiang, S. et al. Activation of WNT7b autocrine eases metastasis of colorectal cancer via epithelial to mesenchymal transition and predicts poor prognosis. BMC Cancer 21, 180 (2021). (PMID: 33607955789375110.1186/s12885-021-07898-2) Acharyya, S. et al. A CXCL1 paracrine network links cancer chemoresistance and metastasis. Cell 150, 165–178 (2012). (PMID: 22770218352801910.1016/j.cell.2012.04.042) Lim, S. Y., Yuzhalin, A. E., Gordon-Weeks, A. N. & Muschel, R. J. Targeting the CCL2-CCR2 signaling axis in cancer metastasis. Oncotarget 7, 28697–28710 (2016). (PMID: 26885690505375610.18632/oncotarget.7376) Johnstone, C. N., Chand, A., Putoczki, T. L. & Ernst, M. Emerging roles for IL-11 signaling in cancer development and progression: focus on breast cancer. Cytokine Growth Factor Rev. 26, 489–498 (2015). (PMID: 2620988510.1016/j.cytogfr.2015.07.015) Hong, C. et al. cGAS-STING drives the IL-6-dependent survival of chromosomally instable cancers. Nature 607, 366–373 (2022). (PMID: 3570580910.1038/s41586-022-04847-2) Adamson, B. et al. A multiplexed single-cell CRISPR screening platform enables systematic dissection of the unfolded protein response. Cell 167, 1867–1882 e1821 (2016). (PMID: 27984733531557110.1016/j.cell.2016.11.048) Haag, S. M. et al. Targeting STING with covalent small-molecule inhibitors. Nature 559, 269–273 (2018). (PMID: 2997372310.1038/s41586-018-0287-8) Dou, Z. et al. Cytoplasmic chromatin triggers inflammation in senescence and cancer. Nature 550, 402–406 (2017). (PMID: 28976970585093810.1038/nature24050) Gui, X. et al. Autophagy induction via STING trafficking is a primordial function of the cGAS pathway. Nature 567, 262–266 (2019). (PMID: 30842662941730210.1038/s41586-019-1006-9) Ishikawa, H., Ma, Z. & Barber, G. N. STING regulates intracellular DNA-mediated, type I interferon-dependent innate immunity. Nature 461, 788–792 (2009). (PMID: 19776740466415410.1038/nature08476) Wang, R. W., Vigano, S., Ben-David, U., Amon, A. & Santaguida, S. Aneuploid senescent cells activate NF-κB to promote their immune clearance by NK cells. EMBO Rep. 22, e52032 (2021). (PMID: 34105235833969010.15252/embr.202052032) Wang, H. et al. cGAS is essential for the antitumor effect of immune checkpoint blockade. Proc. Natl Acad. Sci. USA 114, 1637–1642 (2017). (PMID: 28137885532099410.1073/pnas.1621363114) Ranoa, D. R. E. et al. STING promotes homeostasis via regulation of cell proliferation and chromosomal stability. Cancer Res. 79, 1465–1479 (2019). (PMID: 3048277210.1158/0008-5472.CAN-18-1972) Nassour, J. et al. Autophagic cell death restricts chromosomal instability during replicative crisis. Nature 565, 659–663 (2019). (PMID: 30675059655711810.1038/s41586-019-0885-0) Hu, J. et al. STING inhibits the reactivation of dormant metastasis in lung adenocarcinoma. Nature https://doi.org/10.1038/s41586-023-05880-5 (2023). Rosenthal, R. et al. Neoantigen-directed immune escape in lung cancer evolution. Nature 567, 479–485 (2019). (PMID: 30894752695410010.1038/s41586-019-1032-7) Fujiwara, T. et al. Cytokinesis failure generating tetraploids promotes tumorigenesis in p53-null cells. Nature 437, 1043–1047 (2005). (PMID: 1622230010.1038/nature04217) Ahn, J. et al. Inflammation-driven carcinogenesis is mediated through STING. Nat. Commun. 5, 5166 (2014). (PMID: 2530061610.1038/ncomms6166) Lemos, H. et al. STING promotes the growth of tumors characterized by low antigenicity via IDO activation. Cancer Res. 76, 2076–2081 (2016). (PMID: 26964621487332910.1158/0008-5472.CAN-15-1456) Foijer, F. et al. Chromosome instability induced by Mps1 and p53 mutation generates aggressive lymphomas exhibiting aneuploidy-induced stress. Proc. Natl Acad. Sci. USA 111, 13427–13432 (2014). (PMID: 25197064416994510.1073/pnas.1400892111) Foijer, F. et al. Deletion of the MAD2L1 spindle assembly checkpoint gene is tolerated in mouse models of acute T-cell lymphoma and hepatocellular carcinoma. eLife https://doi.org/10.7554/eLife.20873 (2017). Shoshani, O. et al. Transient genomic instability drives tumorigenesis through accelerated clonal evolution. Genes Dev. 35, 1093–1108 (2021). (PMID: 34266887833689810.1101/gad.348319.121) Frittoli, E. et al. Tissue fluidification promotes a cGAS-STING cytosolic DNA response in invasive breast cancer. Nat. Mater. https://doi.org/10.1038/s41563-022-01431-x (2022). Meric-Bernstam, F. et al. Phase I dose-escalation trial of MIW815 (ADU-S100), an intratumoral STING agonist, in patients with advanced/metastatic solid tumors or lymphomas. Clin. Cancer Res. 28, 677–688 (2022). (PMID: 3471619710.1158/1078-0432.CCR-21-1963) Meric-Bernstam, F. et al. Combination of the STING agonist MIW815 (ADU-S100) and PD-1 inhibitor spartalizumab in advanced/metastatic solid tumors or lymphomas: an open-label, multicenter, phase Ib study. Clin. Cancer Res. 29, 110–121 (2023). (PMID: 3628287410.1158/1078-0432.CCR-22-2235) Lama, L. et al. Development of human cGAS-specific small-molecule inhibitors for repression of dsDNA-triggered interferon expression. Nat. Commun. 10, 2261 (2019). (PMID: 31113940652945410.1038/s41467-019-08620-4) Calvo, V. et al. Discovery of 2-amino-3-amido-5-aryl-pyridines as highly potent, orally bioavailable, and efficacious PERK kinase inhibitors. Bioorg. Med. Chem. Lett. 43, 128058 (2021). (PMID: 3389527610.1016/j.bmcl.2021.128058) Duits, D. E. M., Wellenstein, M. D. & de Visser, K. E. In vitro assessment of cancer cell-induced polarization of macrophages. Methods Enzymol. 632, 133–154 (2020). (PMID: 3200089310.1016/bs.mie.2019.06.011) Tozbikian, G. et al. Mesothelin expression in triple negative breast carcinomas correlates significantly with basal-like phenotype, distant metastases and decreased survival. PLoS ONE 9, e114900 (2014). (PMID: 25506917426661610.1371/journal.pone.0114900) Yarilin, D. et al. Machine-based method for multiplex in situ molecular characterization of tissues by immunofluorescence detection. Sci. Rep. 5, 9534 (2015). (PMID: 25826597482103710.1038/srep09534) Lawrence, M. et al. Software for computing and annotating genomic ranges. PLoS Comput. Biol. 9, e1003118 (2013). (PMID: 23950696373845810.1371/journal.pcbi.1003118) Love, M. I., Huber, W. & Anders, S. Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol. 15, 550 (2014). (PMID: 25516281430204910.1186/s13059-014-0550-8) Efremova, M., Vento-Tormo, M., Teichmann, S. A. & Vento-Tormo, R. CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat. Protoc. 15, 1484–1506 (2020). (PMID: 3210320410.1038/s41596-020-0292-x) Shao, X. et al. CellTalkDB: a manually curated database of ligand-receptor interactions in humans and mice. Brief. Bioinform. https://doi.org/10.1093/bib/bbaa269 (2021). Finak, G. et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data. Genome Biol. 16, 278 (2015). (PMID: 26653891467616210.1186/s13059-015-0844-5) Musa, A. et al. A review of connectivity map and computational approaches in pharmacogenomics. Brief. Bioinform. 18, 903 (2017). (PMID: 28334173611389110.1093/bib/bbx023) Dimitrov, D. et al. Comparison of methods and resources for cell-cell communication inference from single-cell RNA-Seq data. Nat. Commun. 13, 3224 (2022). (PMID: 35680885918452210.1038/s41467-022-30755-0) Browaeys, R., Saelens, W. & Saeys, Y. NicheNet: modeling intercellular communication by linking ligands to target genes. Nat. Methods 17, 159–162 (2020). (PMID: 3181926410.1038/s41592-019-0667-5) Lummertz da Rocha, E. et al. CellComm infers cellular crosstalk that drives haematopoietic stem and progenitor cell development. Nat. Cell Biol. 24, 579–589 (2022). (PMID: 3541402010.1038/s41556-022-00884-1) Guilliams, M. et al. Spatial proteogenomics reveals distinct and evolutionarily conserved hepatic macrophage niches. Cell 185, 379–396 e338 (2022). (PMID: 35021063880925210.1016/j.cell.2021.12.018) Veglia, F., Sanseviero, E. & Gabrilovich, D. I. Myeloid-derived suppressor cells in the era of increasing myeloid cell diversity. Nat. Rev. Immunol. 21, 485–498 (2021). (PMID: 33526920784995810.1038/s41577-020-00490-y) Korsunsky, I. et al. Fast, sensitive and accurate integration of single-cell data with Harmony. Nat. Methods 16, 1289–1296 (2019). (PMID: 31740819688469310.1038/s41592-019-0619-0) Tickle, T., Tirosh, I., Georgescu, C., Brown, M. & Haas, B. inferCNV of the Trinity CTAT Project. Klarman Cell Observatory, Broad Institute of MIT and Harvard, Cambridge, MA, USA (2019). Dann, E., Henderson, N. C., Teichmann, S. A., Morgan, M. D. & Marioni, J. C. Differential abundance testing on single-cell data using k-nearest neighbor graphs. Nat. Biotechnol. https://doi.org/10.1038/s41587-021-01033-z (2021). Elosua-Bayes, M., Nieto, P., Mereu, E., Gut, I. & Heyn, H. SPOTlight: seeded NMF regression to deconvolute spatial transcriptomics spots with single-cell transcriptomes. Nucleic Acids Res. 49, e50 (2021). (PMID: 33544846813677810.1093/nar/gkab043) Jacomy, M., Venturini, T., Heymann, S. & Bastian, M. ForceAtlas2, a continuous graph layout algorithm for handy network visualization designed for the Gephi software. PLoS ONE 9, e98679 (2014). (PMID: 24914678405163110.1371/journal.pone.0098679) Lange, M. et al. CellRank for directed single-cell fate mapping. Nat. Methods 19, 159–170 (2022). Krzywinski, M. et al. Circos: an information aesthetic for comparative genomics. Genome Res. 19, 1639–1645 (2009). (PMID: 19541911275213210.1101/gr.092759.109) Shannon, P. et al. Cytoscape: a software environment for integrated models of biomolecular interaction networks. Genome Res. 13, 2498–2504 (2003). (PMID: 1459765840376910.1101/gr.1239303) |
معلومات مُعتمدة: | R37 CA258829 United States CA NCI NIH HHS; R01 CA280414 United States CA NCI NIH HHS; R21 CA263381 United States CA NCI NIH HHS; R01 CA280572 United States CA NCI NIH HHS; R21 CA266660 United States CA NCI NIH HHS; DP5 OD026395 United States OD NIH HHS; P30 CA008748 United States CA NCI NIH HHS; P50 CA247749 United States CA NCI NIH HHS; United Kingdom WT_ Wellcome Trust; R01 CA266446 United States CA NCI NIH HHS; T32 GM132083 United States GM NIGMS NIH HHS; R01 CA256188 United States CA NCI NIH HHS; U01 CA210152 United States CA NCI NIH HHS |
المشرفين على المادة: | EC 2.7.7.- (cGAS protein, human) 0 (STING1 protein, human) 0 (Interferon Type I) |
تواريخ الأحداث: | Date Created: 20230823 Date Completed: 20230914 Latest Revision: 20240722 |
رمز التحديث: | 20240722 |
مُعرف محوري في PubMed: | PMC10468402 |
DOI: | 10.1038/s41586-023-06464-z |
PMID: | 37612508 |
قاعدة البيانات: | MEDLINE |
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