AIM2 Inhibits BRAF-Mutant Colorectal Cancer Growth in a Caspase-1-Dependent Manner
Open accessAbstract
Absent in melanoma 2 (AIM2), a DNA sensor that plays an important role in natural immunity system, has been reported to participate in colorectal cancer (CRC) development. However, the functional role of AIM2 in BRAF-mutant CRC remains unclear. In this study, we first investigated AIM2 expression level in BRAF-mutant CRC tumor tissues. Overexpression of AIM2 in CRC cells was performed to investigate the effect of AIM2 on CRC cell viability, and cell death detection and caspase activity assay were performed to explore the mechanism that AIM2 impacts the growth of BRAF-mutant CRC cells. Moreover, we confirmed the antitumor effect of AIM2 in BRAF-mutant CRC cell-derived tumor xenograft (CDX) models as well as patient-derived organoids (PDOs). Herein, we reported that AIM2 expression was lower in BRAF-mutant than that in BRAF wild-type CRC tumor tissues. Restoring the expression of AIM2 in BRAF-mutant CRC cells greatly inhibits the tumor cell growth by inducing necrotic cell death. Mechanism studies revealed that AIM2-induced cell death is in a caspase-1-dependent manner. Additionally, overexpression of AIM2 significantly inhibits tumor growth and metastasis in BRAF-mutant CRC in vivo, which was further confirmed in BRAF-mutant CRC PDOs. Taken together, our data suggested that AIM2 inhibits BRAF-mutant colon cancer growth in a caspase-1-dependent manner, which may provide evidence to understand the pathogenesis of CRC with BRAF-mutant, as well as new strategies for manipulation of CRC.
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Prior studies in CRC PDOs have proved them suitable for preclinical drug screening and response prediction.
“Prior studies in CRC PDOs have been proved to be suitable for preclinical drug screening and response prediction (41, 42).”
From Small-molecule PROTAC mediates targeted protein degradation to treat STAT3-dependent epithelial cancer (2022) · cites this paper as [42]
The Results section, “Restoration of AIM2 Expression in BRAF-Mutant CRC Patient-Derived Organoid Inhibits Tumor Growth in vivo” (page unavailable), reports using CRC PDOs to test the effect of AIM2 overexpression on growth. This supports their use as a preclinical experimental model, but the paper does not report drug screening or show that PDOs predict patients’ treatment responses. (LLM, conf=0.82)
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- Authors
- Shah, S., Qin, S., Luo, Y., Huang, Y., Jing, R., Shah, J. N., Chen, J., Chen, H., & Zhong, M.
- Affiliations
- Patan Academy of Health Sciences (NP)
- Shanghai Jiao Tong University (CN)
- Corresponding author
- Chen, Jianjun
- Chen, Huimin
- Zhong, Ming
- ORCID
- Venue
- Frontiers in Cell and Developmental Biology
- Publisher
- Frontiers Media SA
- Published
- 2021-03-25
- Volume
- 9
- Pages
- 588278-588278
- ISSN
- 2296-634X (ISSN-L)
- PMC
- PMC8027362
- OpenAlex
- W3143760270
- Cited by
- 19
- References
- 34
- Citations by year
- 2026: 4 · 2025: 5 · 2024: 4 · 2023: 1 · 2022: 3 · 2021: 2
- FWCI
- 0.78
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Frontiers in Cell and Developmental Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Shanghai International Science and Technology
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Cell death mechanisms and regulation
- Health Sciences › Medicine › Oncology › Colorectal Cancer Treatments and Studies
- Health Sciences › Medicine › Pathology and Forensic Medicine › Genetic factors in colorectal cancer
- Keywords
- AIM2, BRAF mutation, colorectal cancer, caspase-1, necrosis, tumor growth inhibition, metastasis, patient-derived organoids, tumor xenografts, DNA biosensor, innate immunity
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