ArticleThe Journal of cell biology2023
Oncogenic signaling is coupled to colorectal cancer cell differentiation state.
Article in The Journal of cell biology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers.
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Who cites it
7 citing papers in PubMed.
- Microphysiological models of human gastrointestinal diseases.Nature biomedical engineering · 2026Review
- Cell-State-Specific Drug Responses are Associated With Differences in Signaling Network Wiring.Molecular & cellular proteomics : MCP · 2026Article
- Pooled single-cell screen in colorectal cancer defines transcriptional modules linked to oncogenes.Molecular systems biology · 2026Article
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- Application of single-cell sequencing in the study of immune cell infiltration in inflammatory bowel disease and colorectal cancer.World journal of gastrointestinal oncology · 2025Review
- RUCova: Removal of Unwanted Covariance in mass cytometry data.Bioinformatics (Oxford, England) · 2024Article
- Tumor microenvironment characterization in colorectal cancer to identify prognostic and immunotherapy genes signature.BMC cancer · 2023Article
Corrections and comments
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Authors and funding
10 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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Registered trials
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