ArticleNature medicine2015
Modeling colorectal cancer using CRISPR-Cas9-mediated engineering of human intestinal organoids.
Article in Nature medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 625 papers.
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Who cites it
625 citing papers in PubMed, 1,103 citations in OpenAlex.
- Tutorial: interrogating biology using organoid technologies.Nature protocols · 2026Review
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- Translational insights and clinical challenges of targeting cancer stem cells.Signal transduction and targeted therapy · 2026Review
- Lineage plasticity driven by GATA6 loss fuels colorectal cancer metastasis.Cell stem cell · 2026Article
- Harnessing human tumor organoids for cancer modeling and precision therapy.Protein & cell · 2026Review
- Patient-Derived Organoid-Based CRISPR Screens in Cancer Research: Applications, Advances, and Challenges.Cancer medicine · 2026Review
- Current Status of Intestinal Stem Cell Research: Mechanisms, Intestinal Diseases, and Organoid Development.Cells · 2026Review
- Recent advancements and limitations of intestinal organoids for clinical applications.Progress in biomedical engineering (Bristol, England) · 2026Review
- New developments and applications of human organoids.Nature reviews. Molecular cell biology · 2026Review
- Why are Some Tissues More Vulnerable? Revisiting Tissue Specificity in Hereditary Cancer Syndromes.Molecular diagnosis & therapy · 2026Review
- Organoid technology in cancer research.Molecular biomedicine · 2026Review
- Inducing physiological polarity and performing gene editing using CRISPR-Cas9 in human trophoblast organoids.Nature protocols · 2026Review
- Review
- Large-scale, spatially resolved panoramic CRISPR screening in native tissue environments using Perturb-DBiT.Nature biotechnology · 2026Article
- Tumor organoids as a revolutionary platform for advancing cancer nanomedicine.Molecular cancer · 2026Review
- Recurrent COPA mutation drives R-spondin-independent Wnt activation in intestinal tumors.Nature genetics · 2026Article
- Inducible CRISPR/Cas systems in precision oncology: Current applications and future perspectives.Clinical and translational medicine · 2026Review
- Review
- Optimization of RNP-CRISPR for high-efficiency gene editing in mouse intestinal organoids.Molecular and cellular biochemistry · 2026Article
- Monitoring biological effects of somatic cell genome editing.Nature reviews. Genetics · 2026Review
565 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Human colorectal tumors bear recurrent mutations in genes encoding proteins operative in the WNT, MAPK, TGF-β, TP53 and PI3K pathways. Although these pathways influence intestinal stem cell niche signaling, the extent to which mutations in these pathways contribute to human colorectal carcinogenesis remains unclear. Here we use the CRISPR-Cas9 genome-editing system to introduce multiple such mutations into organoids derived from normal human intestinal epithelium. By modulating the culture conditions to mimic that of the intestinal niche, we selected isogenic organoids harboring mutations in the tumor suppressor genes APC, SMAD4 and TP53, and in the oncogenes KRAS and/or PIK3CA. Organoids engineered to express all five mutations grew independently of niche factors in vitro, and they formed tumors after implantation under the kidney subcapsule in mice. Although they formed micrometastases containing dormant tumor-initiating cells after injection into the spleen of mice, they failed to colonize in the liver. In contrast, engineered organoids derived from chromosome-instable human adenomas formed macrometastatic colonies. These results suggest that 'driver' pathway mutations enable stem cell maintenance in the hostile tumor microenvironment, but that additional molecular lesions are required for invasive behavior.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.