ArticleThe Journal of clinical investigation2023
NLRP12 downregulates the Wnt/β-catenin pathway via interaction with STK38 to suppress colorectal cancer.
Article in The Journal of clinical investigation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 30 citations in OpenAlex.
- FBXO17 regulates the malignant progression of colorectal cancer via the Wnt/β-catenin pathway.Translational cancer research · 2026Article
- Homer condensates orchestrate YAP-Wnt signaling crosstalk downstream of the Crumbs polarity complex.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- B3GNT6 suppresses colorectal cancer progression by inhibiting the KRAS/ERK signaling pathway.BMC biotechnology · 2026Article
- STK38-mediated feedback loop regulation of the hedgehog pathway governing tumor heterogeneity in renal papillary carcinoma.Cell death & disease · 2026Article
- NLRPs and tumor: research progress from molecular mechanisms to clinical applications.Oncogene · 2026Review
- NLRP12 in cancer: a context-dependent regulator of tumor progression, immunity, and metabolism.Frontiers in oncology · 2026Review
- Single-cell sequencing and organoids: applications in organ development and disease.Molecular biomedicine · 2025Review
- Article
- Inflammasomes and pyroptosis in cancer: mechanisms and therapeutic advances.Journal of hematology & oncology · 2025Review
- NLRP12 decreases TRIM25-mediated HK2 degradation to promote glycolysis and H3K18la in gastric cancer.Cell death & disease · 2025Article
- Tumoroid Model Reveals Synergistic Impairment of Metabolism by Iron Chelators and Temozolomide in Chemo-Resistant Patient-derived Glioblastoma Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- How ceramides affect the development of colon cancer: from normal colon to carcinoma.Pflugers Archiv : European journal of physiology · 2024Review
- NLRP12/C1qA positive feedback in tumor-associated macrophages regulates immunosuppression through LILRB4/NF-κB pathway in lung adenocarcinoma.Cancer immunology, immunotherapy : CII · 2024Article
- [Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2024Article
- Role of the lncRNA/Wnt signaling pathway in digestive system cancer: a literature review.European journal of medical research · 2024Review
- NLRC5 senses NADCell · 2024Article
- Unlocking hepatocellular carcinoma aggression: STAMBPL1-mediated TRAF2 deubiquitination activates WNT/PI3K/NF-kb signaling pathway.Biology direct · 2024Article
- Discovery of a small-molecule NDR1 agonist for prostate cancer therapy.Frontiers in pharmacology · 2024Article
- Mechanisms of PANoptosis and relevant small-molecule compounds for fighting diseases.Cell death & disease · 2023Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 3 countries.
Funding
Abstract
Colorectal cancer (CRC) at advanced stages is rarely curable, underscoring the importance of exploring the mechanism of CRC progression and invasion. NOD-like receptor family member NLRP12 was shown to suppress colorectal tumorigenesis, but the precise mechanism was unknown. Here, we demonstrate that invasive adenocarcinoma development in Nlrp12-deficient mice is associated with elevated expression of genes involved in proliferation, matrix degradation, and epithelial-mesenchymal transition. Signaling pathway analysis revealed higher activation of the Wnt/β-catenin pathway, but not NF-κB and MAPK pathways, in the Nlrp12-deficient tumors. Using Nlrp12-conditional knockout mice, we revealed that NLRP12 downregulates β-catenin activation in intestinal epithelial cells, thereby suppressing colorectal tumorigenesis. Consistent with this, Nlrp12-deficient intestinal organoids and CRC cells showed increased proliferation, accompanied by higher activation of β-catenin in vitro. With proteomic studies, we identified STK38 as an interacting partner of NLRP12 involved in the inhibition of phosphorylation of GSK3β, leading to the degradation of β-catenin. Consistently, the expression of NLRP12 was significantly reduced, while p-GSK3β and β-catenin were upregulated in mouse and human colorectal tumor tissues. In summary, NLRP12 is a potent negative regulator of the Wnt/β-catenin pathway, and the NLRP12/STK38/GSK3β signaling axis could be a promising therapeutic target for CRC.
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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.