CRISPR-Cas9–mediated gene knockout in intestinal tumor organoids provides functional validation for colorectal cancer driver genes
Open accessAbstract
Significance: Colorectal cancer (CRC) is the third leading cause of cancer-related deaths. Genome sequencing studies have provided comprehensive CRC genomic datasets; however, functional validation for most candidate CRC driver genes has not been performed. Here, we describe a platform for functionally validating CRC driver genes that utilizes CRISPR-Cas9 in mouse intestinal tumor organoids and human CRC-derived organoids. These studies showed Acvr1b , Acvr2a , and Arid2 could function as tumor suppressors in CRC. We also show that co-occurrent mutations in receptors for activin and transforming growth factor-β synergistically promote tumorigenesis, and shed light on the role of activin receptors. This experimental system can also be applied to organoids derived from other organs, which could further contribute to identification of novel cancer driver genes.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
CRISPR cutting screens in 3D organoids have been implemented to explore factors such as growth factor dependency for cell growth, identify potential cancer-driving forces, and uncover key genetic events in cell differentiation.
“Even more exciting is the implementation of CRISPR cutting screens in 3D organoids to explore factors such as growth factor dependency for cell growth14–16, identifying potential cancer-driving forces17–19, and uncovering key genetic events in cell differentiation20–22.”
From Large-scale CRISPR screening in primary human 3D gastric organoids enables comprehensive dissection of gene-drug interactions (2025) · cites this paper as [19]
CRISPR/Cas9 has emerged as an efficient strategy for genome engineering and has been successfully used in model systems, including organoids, to study tumorigenesis.
“CRISPR/Cas9 has emerged as an efficient strategy for genome engineering and has been successfully used in model systems, including organoids, to study tumorigenesis13–16.”
From One-step generation of tumor models by base editor multiplexing in adult stem cell-derived organoids (2023) · cites this paper as [15]
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
No citation lists for this paper
No citation lists for this paper yet — checked again daily.
References 45 · Cited by 172
Research works printed but not linked: 5
- J. L. Bos, ras oncogenes in human cancer: A review. Cancer Res. 49, 4682-4689 (1989).
- J. Bauer, J. C. Sporn, J. Cabral, J. Gomez, B. Jung, Effects of activin and TGFβ on p21 in colon cancer. PLoS One 7, e39381 (2012).
- U. A. Hänninen et al., Exome-wide somatic mutation characterization of small bowel adenocarcinoma. PLoS Genet. 14, e1007200 (2018).
- C. Hodges, J. G. Kirkland, G. R. Crabtree, The many roles of BAF (mSWI/SNF) and PBAF complexes in cancer. Cold Spring Harb. Perspect. Med. 6, a026930 (2016).
- J. J. Staudacher et al., Activin signaling is an essential component of the TGF-β in- duced pro-metastatic phenotype in colorectal cancer. Sci. Rep. 7, 5569 (2017).
- Authors
- Takeda, H., Kataoka, S., Nakayama, M., Ali, M. A. E., Oshima, H., Yamamoto, D., Park, J.-W., Takegami, Y., An, T., Jenkins, N. A., Copeland, N. G., & Oshima, M.
- Affiliations
- Kanazawa University (JP)
- Dnaform (Japan) (JP)
- The University of Texas MD Anderson Cancer Center (US)
- ORCID
- Venue
- Proceedings of the National Academy of Sciences
- Publisher
- National Academy of Sciences
- Published
- 2019-07-12
- Volume
- 116
- Issue
- 31
- Pages
- 15635-15644
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- PMC
- PMC6681705
- OpenAlex
- W2959016616
- Cited by
- 172
- References
- 45
- Citations by year
- 2026: 14 · 2025: 28 · 2024: 31 · 2023: 24 · 2022: 31 · 2021: 23 · 2020: 17 · 2019: 4
- FWCI
- 6.20
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Proceedings of the National Academy of Sciences (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- The Molecular Biology Society of Japan
- Funders
- Naito Foundation
- Japan Agency for Medical Research and Development
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › CRISPR and Genetic Engineering
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Genomics and Diagnostics
- Keywords
- colorectal cancer, driver genes, CRISPR/Cas9 knockout, functional validation, activin receptors, TGF-beta, ACVR1B, ACVR2A, ARID2, tumor suppressor
- MeSH terms
- Animals, Humans, Neoplasm Proteins, Organoids, Colorectal Neoplasms, Mice, Inbred NOD, Gene Expression Profiling, Cell Line, Tumor, Mice, Gene Knockout Techniques, CRISPR-Cas Systems
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
