{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,5]],"date-time":"2026-10-05T20:00:19Z","timestamp":1791230419737,"version":"4.1.0"},"reference-count":62,"publisher":"Rockefeller University Press","issue":"6","license":[{"start":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T00:00:00Z","timestamp":1680652800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.rupress.org\/terms\/"},{"start":{"date-parts":[[2023,10,4]],"date-time":"2023-10-04T00:00:00Z","timestamp":1696377600000},"content-version":"vor","delay-in-days":182,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc-sa\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["RTG2424"],"award-info":[{"award-number":["RTG2424"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001659","name":"Deutsche Forschungsgemeinschaft","doi-asserted-by":"publisher","award":["2783\/5"],"award-info":[{"award-number":["2783\/5"]}],"id":[{"id":"10.13039\/501100001659","id-type":"DOI","asserted-by":"publisher"}]},{"name":"German Ministry of Education and Research","award":["02NUK047E"],"award-info":[{"award-number":["02NUK047E"]}]},{"name":"German Ministry of Education and Research","award":["161 L0220A"],"award-info":[{"award-number":["161 L0220A"]}]},{"name":"German Ministry of Education and Research","award":["16LW0239K"],"award-info":[{"award-number":["16LW0239K"]}]}],"content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2023,6,5]]},"abstract":"<jats:p>Colorectal cancer progression is intrinsically linked to stepwise deregulation of the intestinal differentiation trajectory. In this process, sequential mutations of APC, KRAS, TP53, and SMAD4 enable oncogenic signaling and establish the hallmarks of cancer. Here, we use mass cytometry of isogenic human colon organoids and patient-derived cancer organoids to capture oncogenic signaling, cell phenotypes, and differentiation states in a high-dimensional single-cell map. We define a differentiation axis in all tumor progression states from normal to cancer. Our data show that colorectal cancer driver mutations shape the distribution of cells along the differentiation axis. In this regard, subsequent mutations can have stem cell promoting or restricting effects. Individual nodes of the cancer cell signaling network remain coupled to the differentiation state, regardless of the presence of driver mutations. We use single-cell RNA sequencing to link the (phospho-)protein signaling network to transcriptomic states with biological and clinical relevance. Our work highlights how oncogenes gradually shape signaling and transcriptomes during tumor progression.<\/jats:p>","DOI":"10.1083\/jcb.202204001","type":"journal-article","created":{"date-parts":[[2023,3,18]],"date-time":"2023-03-18T02:21:01Z","timestamp":1679106061000},"update-policy":"https:\/\/doi.org\/10.1083\/jcb.crossmarkpolicy","source":"Crossref","is-referenced-by-count":16,"title":["Oncogenic signaling is coupled to colorectal cancer cell differentiation state"],"prefix":"10.1083","volume":"222","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5138-3967","authenticated-orcid":true,"given":"Thomas","family":"Sell","sequence":"first","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathology 1 , , Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin 1 , , Berlin, Germany"},{"name":"Institute of Biology, Humboldt University of Berlin 2 , Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2609-9654","authenticated-orcid":true,"given":"Christian","family":"Klotz","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/01k5qnb77","id-type":"ROR","asserted-by":"publisher"}],"name":"Department of Infectious Diseases, Robert Koch-Institute 3 , , Berlin, Germany"},{"name":"Unit 16 Mycotic and Parasitic Agents and Mycobacteria 3 , , Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5433-9956","authenticated-orcid":true,"given":"Matthias M.","family":"Fischer","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathology 1 , , Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin 1 , , Berlin, Germany"},{"name":"Institute of Biology, Humboldt University of Berlin 2 , Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1179-4080","authenticated-orcid":true,"given":"Rosario","family":"Astaburuaga-Garc\u00eda","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathology 1 , , Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin 1 , , Berlin, Germany"},{"name":"Institute of Biology, Humboldt University of Berlin 2 , Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1293-2484","authenticated-orcid":true,"given":"Susanne","family":"Krug","sequence":"additional","affiliation":[{"name":"Department of Gastroenterology, Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin, Rheumatology and Infectious Diseases, Clinical Physiology\/Nutritional Medicine 4 , Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2941-6179","authenticated-orcid":true,"given":"Jarno","family":"Drost","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/02aj7yc53","id-type":"ROR","asserted-by":"publisher"}],"name":"Princess M\u00e1xima Center for Pediatric Oncology 5 , Utrecht, Netherlands"},{"name":"Oncode Institute 6 , Utrecht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3077-5582","authenticated-orcid":true,"given":"Hans","family":"Clevers","sequence":"additional","affiliation":[{"name":"Oncode Institute 6 , Utrecht, Netherlands"},{"id":[{"id":"https:\/\/ror.org\/023qc4a07","id-type":"ROR","asserted-by":"publisher"}],"name":"Hubrecht Institute, Royal Netherlands Academy of Arts and Sciences and University Medical Center Utrecht 7 , Utrecht, Netherlands"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6219-1514","authenticated-orcid":true,"given":"Christine","family":"Sers","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathology 1 , , Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin 1 , , Berlin, Germany"},{"name":"Institute of Biology, Humboldt University of Berlin 2 , Berlin, Germany"},{"name":"German Cancer Consortium Partner Site Berlin, German Cancer Research Center 8 , Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2553-9999","authenticated-orcid":true,"given":"Markus","family":"Morkel","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathology 1 , , Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin 1 , , Berlin, Germany"},{"name":"German Cancer Consortium Partner Site Berlin, German Cancer Research Center 8 , Heidelberg, Germany"},{"name":"Berlin Institute of Health at Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, Bioportal Single Cells 9 , Berlin, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0171-7447","authenticated-orcid":true,"given":"Nils","family":"Bl\u00fcthgen","sequence":"additional","affiliation":[{"id":[{"id":"https:\/\/ror.org\/001w7jn25","id-type":"ROR","asserted-by":"publisher"}],"name":"Institute of Pathology 1 , , Berlin, Germany"},{"name":"Charit\u00e9\u2014Universit\u00e4tsmedizin Berlin, corporate member of Freie Universit\u00e4t Berlin and Humboldt-Universit\u00e4t zu Berlin 1 , , Berlin, Germany"},{"name":"Institute of Biology, Humboldt University of Berlin 2 , Berlin, Germany"},{"name":"German Cancer Consortium Partner Site Berlin, German Cancer Research Center 8 , Heidelberg, Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2023,4,5]]},"reference":[{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"1052","DOI":"10.1038\/s43018-022-00402-0","article-title":"Mex3a marks drug-tolerant persister colorectal cancer cells that mediate relapse after chemotherapy","volume":"3","author":"\u00c1lvarez-Varela","year":"2022","journal-title":"Nat. Cancer"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"121","DOI":"10.1038\/s41586-019-1154-y","article-title":"Single-cell transcriptomes of the regenerating intestine reveal a revival stem cell","volume":"569","author":"Ayyaz","year":"2019","journal-title":"Nature"},{"key":"2023040513310212800_","first-page":"7717","article-title":"p53 gene mutations occur in combination with 17p allelic deletions as late events in colorectal tumorigenesis","volume":"50","author":"Baker","year":"1990","journal-title":"Cancer Res."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"6813","DOI":"10.1021\/ac901049w","article-title":"Mass cytometry: Technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry","volume":"81","author":"Bandura","year":"2009","journal-title":"Anal. Chem."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"1003","DOI":"10.1038\/nature06196","article-title":"Identification of stem cells in small intestine and colon by marker gene Lgr5","volume":"449","author":"Barker","year":"2007","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"801","DOI":"10.1016\/j.stem.2017.02.007","article-title":"Mex3a marks a slowly dividing subpopulation of Lgr5+ intestinal stem cells","volume":"20","author":"Barriga","year":"2017","journal-title":"Cell Stem Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1016\/s0092-8674(02)01015-2","article-title":"Beta-catenin and TCF mediate cell positioning in the intestinal epithelium by controlling the expression of EphB\/ephrinB","volume":"111","author":"Batlle","year":"2002","journal-title":"Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"1126","DOI":"10.1038\/nature03626","article-title":"EphB receptor activity suppresses colorectal cancer progression","volume":"435","author":"Batlle","year":"2005","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"78","DOI":"10.1038\/s41593-018-0290-2","article-title":"Human microglia regional heterogeneity and phenotypes determined by multiplexed single-cell mass cytometry","volume":"22","author":"B\u00f6ttcher","year":"2019","journal-title":"Nat. Neurosci."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"2919","DOI":"10.1038\/s41467-019-10954-y","article-title":"Cell type-dependent differential activation of ERK by oncogenic KRAS in colon cancer and intestinal epithelium","volume":"10","author":"Brandt","year":"2019","journal-title":"Nat. Commun."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"603","DOI":"10.1038\/s41586-022-05402-9","article-title":"Metastatic recurrence in colorectal cancer arises from residual EMP1+ cells","volume":"611","author":"Ca\u00f1ellas-Socias","year":"2022","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"330","DOI":"10.1038\/nature11252","article-title":"Comprehensive molecular characterization of human colon and rectal cancer","volume":"487","author":"Cancer Genome Atlas Network","year":"2012","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"612","DOI":"10.1016\/j.cels.2018.02.010","article-title":"Compensation of signal spillover in suspension and imaging mass cytometry","volume":"6","author":"Chevrier","year":"2018","journal-title":"Cell Syst."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"379","DOI":"10.1007\/s10565-008-9092-8","article-title":"Role of PARP-1 and PARP-2 in the expression of apoptosis-regulating genes in HeLa cells","volume":"25","author":"Cohausz","year":"2009","journal-title":"Cell Biol. Toxicol."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1016\/j.acha.2006.04.006","article-title":"Diffusion maps","volume":"21","author":"Coifman","year":"2006","journal-title":"Appl. Comput. Harmon. Anal."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"869","DOI":"10.15252\/emmm.201707550","article-title":"A genome editing approach to study cancer stem cells in human tumors","volume":"9","author":"Cortina","year":"2017","journal-title":"EMBO Mol. Med."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"43","DOI":"10.1038\/nature14415","article-title":"Sequential cancer mutations in cultured human intestinal stem cells","volume":"521","author":"Drost","year":"2015","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1146\/annurev-pathol-011110-130235","article-title":"Molecular genetics of colorectal cancer","volume":"6","author":"Fearon","year":"2011","journal-title":"Annu. Rev. Pathol."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"759","DOI":"10.1016\/0092-8674(90)90186-i","article-title":"A genetic model for colorectal tumorigenesis","volume":"61","author":"Fearon","year":"1990","journal-title":"Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"489","DOI":"10.1038\/msb.2011.27","article-title":"Strong negative feedback from Erk to Raf confers robustness to MAPK signalling","volume":"7","author":"Fritsche-Guenther","year":"2011","journal-title":"Mol. Syst. Biol."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"255ra131","DOI":"10.1126\/scitranslmed.3009701","article-title":"Clinical recovery from surgery correlates with single-cell immune signatures","volume":"6","author":"Gaudilli\u00e8re","year":"2014","journal-title":"Sci. Transl. Med."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"367","DOI":"10.1186\/1471-2105-11-367","article-title":"A flexible R package for nonnegative matrix factorization","volume":"11","author":"Gaujoux","year":"2010","journal-title":"BMC Bioinformatics"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"715","DOI":"10.1038\/nature15382","article-title":"Yap-dependent reprogramming of Lgr5(+) stem cells drives intestinal regeneration and cancer","volume":"526","author":"Gregorieff","year":"2015","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1158\/2159-8290.cd-21-1059","article-title":"Hallmarks of cancer: New dimensions","volume":"12","author":"Hanahan","year":"2022","journal-title":"Cancer Discov."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"3573","DOI":"10.1016\/j.cell.2021.04.048","article-title":"Integrated analysis of multimodal single-cell data","volume":"184","author":"Hao","year":"2021","journal-title":"Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"502","DOI":"10.1080\/01621459.1989.10478797","article-title":"Principal curves","volume":"84","author":"Hastie","year":"1989","journal-title":"J. Am. Stat. Assoc."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"740","DOI":"10.1016\/j.cell.2016.06.017","article-title":"A landscape of pharmacogenomic interactions in cancer","volume":"166","author":"Iorio","year":"2016","journal-title":"Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"127","DOI":"10.1159\/000151359","article-title":"Serrated adenoma of the colorectum undergoes a proliferation versus differentiation process: New conceptual interpretation of morphogenesis","volume":"74","author":"Jiao","year":"2008","journal-title":"Oncology"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"963","DOI":"10.1038\/s41588-022-01100-4","article-title":"Single-cell and bulk transcriptome sequencing identifies two epithelial tumor cell states and refines the consensus molecular classification of colorectal cancer","volume":"54","author":"Joanito","year":"2022","journal-title":"Nat. Genet."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"979","DOI":"10.1016\/j.stemcr.2015.10.003","article-title":"Isolation of human colon stem cells using surface expression of PTK7","volume":"5","author":"Jung","year":"2015","journal-title":"Stem Cell Rep."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"368","DOI":"10.1038\/384368a0","article-title":"Decreased apoptosis in the brain and premature lethality in CPP32-deficient mice","volume":"384","author":"Kuida","year":"1996","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"116","DOI":"10.1186\/s12915-020-00844-x","article-title":"Malignant transformation and genetic alterations are uncoupled in early colorectal cancer progression","volume":"18","author":"Mamlouk","year":"2020","journal-title":"BMC Biol."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","DOI":"10.48550\/arXiv.1802.03426","article-title":"UMAP: Uniform manifold approximation and projection for dimension reduction","author":"McInnes","year":"2018","journal-title":"arXiv"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"511","DOI":"10.1016\/j.stem.2011.02.020","article-title":"The intestinal stem cell signature identifies colorectal cancer stem cells and predicts disease relapse","volume":"8","author":"Merlos-Su\u00e1rez","year":"2011","journal-title":"Cell Stem Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"3079","DOI":"10.1038\/emboj.2012.166","article-title":"The Lgr5 intestinal stem cell signature: Robust expression of proposed quiescent \u201c+4\u201d cell markers","volume":"31","author":"Mu\u00f1oz","year":"2012","journal-title":"EMBO J."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"421","DOI":"10.1016\/j.celrep.2013.09.005","article-title":"Identification of Lgr5-independent spheroid-generating progenitors of the mouse fetal intestinal epithelium","volume":"5","author":"Mustata","year":"2013","journal-title":"Cell Rep."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"701","DOI":"10.1038\/nm.1951","article-title":"Sustained in vitro intestinal epithelial culture within a Wnt-dependent stem cell niche","volume":"15","author":"Ootani","year":"2009","journal-title":"Nat. Med."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"1","DOI":"10.1016\/j.jim.2010.07.002","article-title":"Highly multiparametric analysis by mass cytometry","volume":"361","author":"Ornatsky","year":"2010","journal-title":"J. Immunol. Methods"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"13824","DOI":"10.1038\/ncomms13824","article-title":"BMP restricts stemness of intestinal Lgr5+ stem cells by directly suppressing their signature genes","volume":"8","author":"Qi","year":"2017","journal-title":"Nat. Commun."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"335","DOI":"10.1038\/s41592-020-0737-8","article-title":"Cell-type-specific signaling networks in heterocellular organoids","volume":"17","author":"Qin","year":"2020","journal-title":"Nat. Methods"},{"key":"2023040513310212800_","article-title":"R: A Language and Environment for Statistical Computing","author":"R Core Team","year":"2020","journal-title":"R Found. Stat. Comput."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"934","DOI":"10.1038\/418934a","article-title":"Tumorigenesis: RAF\/RAS oncogenes and mismatch-repair status","volume":"418","author":"Rajagopalan","year":"2002","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"262","DOI":"10.1038\/nature07935","article-title":"Single Lgr5 stem cells build crypt-villus structures in vitro without a mesenchymal niche","volume":"459","author":"Sato","year":"2009","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"415","DOI":"10.1038\/nature09637","article-title":"Paneth cells constitute the niche for Lgr5 stem cells in intestinal crypts","volume":"469","author":"Sato","year":"2010","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"1762","DOI":"10.1053\/j.gastro.2011.07.050","article-title":"Long-term expansion of epithelial organoids from human colon, adenoma, adenocarcinoma, and Barrett\u2019s epithelium","volume":"141","author":"Sato","year":"2011","journal-title":"Gastroenterology"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"14262","DOI":"10.1038\/ncomms14262","article-title":"Molecular dissection of colorectal cancer in pre-clinical models identifies biomarkers predicting sensitivity to EGFR inhibitors","volume":"8","author":"Sch\u00fctte","year":"2017","journal-title":"Nat. Commun."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"20","DOI":"10.1038\/s41467-017-02391-6","article-title":"Perturbation-response genes reveal signaling footprints in cancer gene expression","volume":"9","author":"Schubert","year":"2018","journal-title":"Nat. Commun."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"93","DOI":"10.1016\/j.ccr.2012.11.014","article-title":"Loss of p53 in enterocytes generates an inflammatory microenvironment enabling invasion and lymph node metastasis of carcinogen-induced colorectal tumors","volume":"23","author":"Schwitalla","year":"2013","journal-title":"Cancer Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"66","DOI":"10.1038\/s41586-019-1146-y","article-title":"Self-organization and symmetry breaking in intestinal organoid development","volume":"569","author":"Serra","year":"2019","journal-title":"Nature"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"714","DOI":"10.1016\/j.cell.2019.06.029","article-title":"Intra- and inter-cellular rewiring of the human colon during ulcerative colitis","volume":"178","author":"Smillie","year":"2019","journal-title":"Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"780","DOI":"10.1016\/j.cell.2016.04.019","article-title":"Mass cytometry: Single cells, many features","volume":"165","author":"Spitzer","year":"2016","journal-title":"Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"4897","DOI":"10.1038\/s41596-021-00603-4","article-title":"Multiplexed single-cell analysis of organoid signaling networks","volume":"16","author":"Sufi","year":"2021","journal-title":"Nat. Protoc."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"189","DOI":"10.1126\/science.aad0501","article-title":"Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq","volume":"352","author":"Tirosh","year":"2016","journal-title":"Science"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","DOI":"10.15252\/emmm.202114123","article-title":"Mitogen-activated protein kinase activity drives cell trajectories in colorectal cancer","volume":"13","author":"Uhlitz","year":"2021","journal-title":"EMBO Mol. Med."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"241","DOI":"10.1016\/s0092-8674(02)01014-0","article-title":"The beta-catenin\/TCF-4 complex imposes a crypt progenitor phenotype on colorectal cancer cells","volume":"111","author":"van de Wetering","year":"2002","journal-title":"Cell"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"2884","DOI":"10.1016\/j.jmb.2019.05.031","article-title":"Establishing pure cancer organoid cultures: Identification, selection and verification of cancer phenotypes and genotypes","volume":"431","author":"Wallaschek","year":"2019","journal-title":"J. Mol. Biol."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"1304","DOI":"10.1016\/j.celrep.2018.10.001","article-title":"Comprehensive molecular characterization of the hippo signaling pathway in cancer","volume":"25","author":"Wang","year":"2018","journal-title":"Cell Rep."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"1686","DOI":"10.21105\/joss.01686","article-title":"Welcome to the tidyverse","volume":"4","author":"Wickham","year":"2019","journal-title":"J. Open Source Softw."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"685","DOI":"10.1002\/cyto.a.23495","article-title":"Tellurium-based mass cytometry barcode for live and fixed cells","volume":"93","author":"Willis","year":"2018","journal-title":"Cytometry A"},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"806","DOI":"10.1101\/gad.12.6.806","article-title":"Essential contribution of caspase 3\/CPP32 to apoptosis and its associated nuclear changes","volume":"12","author":"Woo","year":"1998","journal-title":"Genes Dev."},{"key":"2023040513310212800_","doi-asserted-by":"publisher","first-page":"2197","DOI":"10.1038\/s41467-019-09898-0","article-title":"MEK inhibitors activate Wnt signalling and induce stem cell plasticity in colorectal cancer","volume":"10","author":"Zhan","year":"2019","journal-title":"Nat. Commun"}],"container-title":["Journal of Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/doi\/10.1083\/jcb.202204001\/1450400\/jcb_202204001.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/rupress.org\/jcb\/article-pdf\/doi\/10.1083\/jcb.202204001\/1450400\/jcb_202204001.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,4,5]],"date-time":"2023-04-05T09:32:45Z","timestamp":1680687165000},"score":1,"resource":{"primary":{"URL":"https:\/\/rupress.org\/jcb\/article\/222\/6\/e202204001\/213999\/Oncogenic-signaling-is-coupled-to-colorectal"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,4,5]]},"references-count":62,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2023,6,5]]}},"URL":"https:\/\/doi.org\/10.1083\/jcb.202204001","relation":{},"ISSN":["0021-9525","1540-8140"],"issn-type":[{"value":"0021-9525","type":"print"},{"value":"1540-8140","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,4,5]]},"article-number":"e202204001"}}