ArticleThe Journal of experimental medicine2020
AKT-dependent NOTCH3 activation drives tumor progression in a model of mesenchymal colorectal cancer.
Article in The Journal of experimental medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
61 citing papers in PubMed, 101 citations in OpenAlex.
- NICD3 mediates pro-angiogenic effects through SMAD3/TGFBI axis in colorectal cancer.Cell death & disease · 2026Article
- Decoding notch signaling pathway: an updated insight into its role in colorectal cancer progression and therapy.Cancer cell international · 2026Review
- Novel Syngeneic Cell Lines for Studying High-Risk BRAFV600E-Driven Colorectal Cancer In Vivo.Cancer research communications · 2026Article
- Notch3 regulates pericyte phenotypic plasticity in colorectal cancer.Communications biology · 2026Article
- The dual role of the Notch signaling pathway in digestive system cancers.European journal of medical research · 2026Review
- Bridging aging and colorectal cancer: synergistic roles of inflammaging and immunosenescence.Frontiers in immunology · 2026Review
- The immune microenvironment of colorectal cancer.Nature reviews. Cancer · 2025Review
- The aggressive colorectal cancer subtype marker HTR2B has a dual role depending on the tumor microenvironment.Cell communication and signaling : CCS · 2025Article
- Role of Notch gene receptors as prognostic biomarkers in colorectal cancer.Scientific reports · 2025Article
- Preclinical models in the study of lymph node metastasis.Journal of Zhejiang University. Science. B · 2025Review
- Hepatic iNKT cells facilitate colorectal cancer metastasis by inducing a fibrotic niche in the liver.iScience · 2025Article
- Enhancing doxorubicin's anticancer impact in colorectal cancer by targeting the Akt/Gsk3β/mTOR-SREBP1 signaling axis with an HDAC inhibitor.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2025Article
- LIN28B-mediated PI3K/AKT pathway activation promotes metastasis in colorectal cancer models.The Journal of clinical investigation · 2025Article
- Notch signaling in the tumor immune microenvironment of colorectal cancer: mechanisms and therapeutic opportunities.Journal of translational medicine · 2025Review
- Notch signaling in cancers: mechanism and potential therapy.Frontiers in cell and developmental biology · 2025Review
- USP10 drives cancer stemness and enables super-competitor signalling in colorectal cancer.Oncogene · 2024Article
- Mechanics-activated fibroblasts promote pulmonary group 2 innate lymphoid cell plasticity propelling silicosis progression.Nature communications · 2024Article
- Perivascular NOTCH3+ Stem Cells Drive Meningioma Tumorigenesis and Resistance to Radiotherapy.Cancer discovery · 2024Article
- Article
- A NOTCH3-CXCL12-driven myeloma-tumor niche signaling axis promotes chemoresistance in multiple myeloma.Haematologica · 2024Article
1 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
20 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recently, a transcriptome-based consensus molecular subtype (CMS) classification of colorectal cancer (CRC) has been established, which may ultimately help to individualize CRC therapy. However, the lack of animal models that faithfully recapitulate the different molecular subtypes impedes adequate preclinical testing of stratified therapeutic concepts. Here, we demonstrate that constitutive AKT activation in intestinal epithelial cells markedly enhances tumor invasion and metastasis in Trp53ΔIEC mice (Trp53ΔIECAktE17K) upon challenge with the carcinogen azoxymethane. Gene-expression profiling indicates that Trp53ΔIECAktE17K tumors resemble the human mesenchymal colorectal cancer subtype (CMS4), which is characterized by the poorest survival rate among the four CMSs. Trp53ΔIECAktE17K tumor cells are characterized by Notch3 up-regulation, and treatment of Trp53ΔIECAktE17K mice with a NOTCH3-inhibiting antibody reduces invasion and metastasis. In CRC patients, NOTCH3 expression correlates positively with tumor grading and the presence of lymph node as well as distant metastases and is specifically up-regulated in CMS4 tumors. Therefore, we suggest NOTCH3 as a putative target for advanced CMS4 CRC patients.
Indexed as
Identifiers
What OpenQuestion holds
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.