دورية أكاديمية
Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities.
العنوان: | Combined Proteomic and Genetic Interaction Mapping Reveals New RAS Effector Pathways and Susceptibilities. |
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المؤلفون: | Kelly MR; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, California.; Program in Cancer Biology, Stanford University School of Medicine, Stanford, California., Kostyrko K; Division of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, California., Han K; Department of Genetics, Stanford University School of Medicine, Stanford, California., Mooney NA; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, California., Jeng EE; Department of Genetics, Stanford University School of Medicine, Stanford, California., Spees K; Department of Genetics, Stanford University School of Medicine, Stanford, California., Dinh PT; Division of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, California., Abbott KL; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, California., Gwinn DM; Division of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, California., Sweet-Cordero EA; Division of Hematology and Oncology, Department of Pediatrics, University of California, San Francisco, San Francisco, California. pjackson@stanford.edu bassik@stanford.edu Alejandro.Sweet-Cordero@ucsf.edu., Bassik MC; Department of Genetics, Stanford University School of Medicine, Stanford, California. pjackson@stanford.edu bassik@stanford.edu Alejandro.Sweet-Cordero@ucsf.edu.; Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, California., Jackson PK; Baxter Laboratory, Department of Microbiology & Immunology, Stanford University School of Medicine, Stanford, California. pjackson@stanford.edu bassik@stanford.edu Alejandro.Sweet-Cordero@ucsf.edu.; Chemistry, Engineering, and Medicine for Human Health (ChEM-H), Stanford University, Stanford, California.; Department of Pathology, Stanford University School of Medicine, Stanford, California. |
المصدر: | Cancer discovery [Cancer Discov] 2020 Dec; Vol. 10 (12), pp. 1950-1967. Date of Electronic Publication: 2020 Jul 29. |
نوع المنشور: | Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't |
اللغة: | English |
بيانات الدورية: | Publisher: American Association for Cancer Research Country of Publication: United States NLM ID: 101561693 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2159-8290 (Electronic) Linking ISSN: 21598274 NLM ISO Abbreviation: Cancer Discov Subsets: MEDLINE |
أسماء مطبوعة: | Original Publication: Philadelphia, PA : American Association for Cancer Research |
مواضيع طبية MeSH: | Lung Neoplasms/*genetics , Proteomics/*methods , ras Proteins/*genetics, Humans |
مستخلص: | Activating mutations in RAS GTPases drive many cancers, but limited understanding of less-studied RAS interactors, and of the specific roles of different RAS interactor paralogs, continues to limit target discovery. We developed a multistage discovery and screening process to systematically identify genes conferring RAS-related susceptibilities in lung adenocarcinoma. Using affinity purification mass spectrometry, we generated a protein-protein interaction map of RAS interactors and pathway components containing hundreds of interactions. From this network, we constructed a CRISPR dual knockout library targeting 119 RAS-related genes that we screened for KRAS -dependent genetic interactions (GI). This approach identified new RAS effectors, including the adhesion controller RADIL and the endocytosis regulator RIN1, and >250 synthetic lethal GIs, including a potent KRAS -dependent interaction between RAP1GDS1 and RHOA. Many GIs link specific paralogs within and between gene families. These findings illustrate the power of multiomic approaches to uncover synthetic lethal combinations specific for hitherto untreatable cancer genotypes. SIGNIFICANCE: We establish a deep network of protein-protein and genetic interactions in the RAS pathway. Many interactions validated here demonstrate important specificities and redundancies among paralogous RAS regulators and effectors. By comparing synthetic lethal interactions across KRAS -dependent and KRAS -independent cell lines, we identify several new combination therapy targets for RAS-driven cancers. This article is highlighted in the In This Issue feature, p. 1775 . (©2020 American Association for Cancer Research.) |
References: | Cell. 2011 May 13;145(4):513-28. (PMID: 21565611) Mol Cell Biol. 1995 Mar;15(3):1318-23. (PMID: 7862125) PLoS Pathog. 2016 Oct 5;12(10):e1005929. (PMID: 27706223) Cancer Cell. 2005 Mar;7(3):219-26. (PMID: 15766660) Cancer Res. 2018 Aug 15;78(16):4658-4670. (PMID: 29871936) Genes Dev. 2011 Nov 15;25(22):2347-60. (PMID: 22085962) Cell. 2015 Dec 3;163(6):1515-26. (PMID: 26627737) Cancer Discov. 2016 Mar;6(3):316-29. (PMID: 26739882) Methods Mol Biol. 2011;769:25-30. (PMID: 21748666) Oncotarget. 2019 Aug 27;10(50):5126-5135. (PMID: 31497244) J Mol Med (Berl). 2016 Feb;94(2):121-35. (PMID: 26526121) Science. 2002 Jul 5;297(5578):63-4. (PMID: 12098689) J Biol Chem. 2011 Apr 8;286(14):12141-8. (PMID: 21242305) Science. 2004 Jul 16;305(5682):399-401. (PMID: 15256671) Proc Natl Acad Sci U S A. 1994 Jun 21;91(13):5982-6. (PMID: 8016101) J Biol Chem. 2014 Mar 7;289(10):6862-6876. (PMID: 24415755) Nat Rev Cancer. 2015 Oct;15(10):577-92. (PMID: 26399658) Clin Cancer Res. 2011 Oct 15;17(20):6482-9. (PMID: 21831957) Nature. 2002 Dec 12;420(6916):629-35. (PMID: 12478284) Proc Natl Acad Sci U S A. 2018 Sep 18;115(38):9563-9568. (PMID: 30190425) Oncogene. 1998 Sep 17;17(11 Reviews):1415-38. (PMID: 9779988) J Cell Biol. 2012 Dec 10;199(6):951-67. (PMID: 23209302) Genes Cancer. 2011 Mar;2(3):216-31. (PMID: 21779495) Nature. 1998 Jul 16;394(6690):295-9. (PMID: 9685162) Biochemistry. 2010 Mar 9;49(9):1970-4. (PMID: 20131908) Nat Protoc. 2014 Jan;9(1):182-92. (PMID: 24385148) Nat Methods. 2020 Mar;17(3):261-272. (PMID: 32015543) Nucleic Acids Res. 2017 Jan 4;45(D1):D369-D379. (PMID: 27980099) Cell. 2017 Feb 23;168(5):890-903.e15. (PMID: 28162770) J Biol Chem. 2010 Nov 12;285(46):35255-66. (PMID: 20709748) Small GTPases. 2014;5:e29846. (PMID: 25010901) Proc Natl Acad Sci U S A. 2020 Feb 18;117(7):3627-3636. (PMID: 32019878) Cancer Discov. 2012 May;2(5):401-4. (PMID: 22588877) Nature. 2014 Nov 20;515(7527):443-7. (PMID: 25219851) Assay Drug Dev Technol. 2015 Sep;13(7):347-55. (PMID: 26267765) Cancer Cell. 2012 Feb 14;21(2):147-9. (PMID: 22340588) Nature. 2013 May 30;497(7451):633-7. (PMID: 23665962) EMBO J. 2008 Sep 17;27(18):2375-87. (PMID: 18756269) Cancer Cell. 2014 Mar 17;25(3):272-81. (PMID: 24651010) Nat Rev Cancer. 2005 Sep;5(9):689-98. (PMID: 16110319) Maturitas. 2015 May;81(1):5-9. (PMID: 25708226) EMBO J. 1998 Dec 1;17(23):6776-82. (PMID: 9843482) Dev Cell. 2017 Oct 9;43(1):6-9. (PMID: 29017030) Cancer Discov. 2018 Nov;8(11):1474-1489. (PMID: 30209081) Genome Res. 2008 Apr;18(4):644-52. (PMID: 18381899) Cell. 2017 Jul 27;170(3):564-576.e16. (PMID: 28753430) Genes Cancer. 2011 Mar;2(3):275-87. (PMID: 21779498) Dev Cell. 2001 Jul;1(1):73-82. (PMID: 11703925) Nat Biotechnol. 2016 Jun;34(6):634-6. (PMID: 27159373) RNA. 2003 Apr;9(4):493-501. (PMID: 12649500) Mol Biol Cell. 2012 Dec;23(24):4751-65. (PMID: 23097489) Nat Cell Biol. 2018 Sep;20(9):1064-1073. (PMID: 30104724) Cytoskeleton (Hoboken). 2010 Sep;67(9):545-54. (PMID: 20803696) Nature. 1982 Nov 11;300(5888):149-52. (PMID: 7133135) Nat Biotechnol. 2017 May;35(5):463-474. (PMID: 28319085) Cancer Cell. 2013 Jul 8;24(1):59-74. (PMID: 23845442) Nat Methods. 2017 Jun;14(6):573-576. (PMID: 28319113) J Biol Chem. 2019 Aug 2;294(31):11793-11804. (PMID: 31197034) Dev Cell. 2017 Jul 10;42(1):22-36.e12. (PMID: 28625565) Nat Genet. 2019 Sep;51(9):1308-1314. (PMID: 31406347) Proteomics. 2009 May;9(10):2888-91. (PMID: 19405035) |
معلومات مُعتمدة: | U01 CA199216 United States CA NCI NIH HHS |
المشرفين على المادة: | EC 3.6.5.2 (ras Proteins) |
تواريخ الأحداث: | Date Created: 20200731 Date Completed: 20211124 Latest Revision: 20230331 |
رمز التحديث: | 20240628 |
مُعرف محوري في PubMed: | PMC7710624 |
DOI: | 10.1158/2159-8290.CD-19-1274 |
PMID: | 32727735 |
قاعدة البيانات: | MEDLINE |
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