ArticleCell death & disease2022
KIT promotes tumor stroma formation and counteracts tumor-suppressive TGFβ signaling in colorectal cancer.
Article in Cell death & disease, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 15 citations in OpenAlex.
- Activation of KIT signaling promotes early tumorigenesis through the AP-1 pathway in APC/TP53 double-knockout human colon organoids.Cell death & disease · 2026Article
- Integrated multi-omics profiling identifies genetic loci of African swine fever resistance in pigs.GigaScience · 2026Article
- Improved protein binder design using β-pairing targeted RFdiffusion.Nature communications · 2026Article
- Double jeopardy: howFrontiers in cell and developmental biology · 2026Review
- Analysis of experimental colorectal liver metastases identifies distinct proliferation-independent transcriptional programs in micro- versus macrometastases.Journal of translational medicine · 2025Article
- c-KitCell death and differentiation · 2025Article
- Identification of the "Collagen-Macrophage" sub-category of patients with colorectal cancer as an extension of the CMS4 subtype with THBS2 as a therapeutic target.BMC gastroenterology · 2025Article
- Prognostic implications and therapeutic opportunities related to CAF subtypes in CMS4 colorectal cancer: insights from single-cell and bulk transcriptomics.Apoptosis : an international journal on programmed cell death · 2025Article
- AMIGO2 enhances the invasive potential of colorectal cancer by inducing EMT.Cancer gene therapy · 2024Article
- The Innate Immune System Surveillance Biomarker p87 in African Americans and Caucasians with Small High-Grade Dysplastic Adenoma [SHiGDA] and Right-SidedGastrointestinal disorders (Basel, Switzerland) · 2024Article
- Clinical Challenges of Consensus Molecular Subtype CMS4 Colon Cancer in the Era of Precision Medicine.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Review
- Article
- Human patient derived organoids: an emerging precision medicine model for gastrointestinal cancer research.Frontiers in cell and developmental biology · 2024Review
- Analyzing aberrant DNA methylation in colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients.Scientific reports · 2023Article
- Analyzing aberrant DNA methylation in Colorectal cancer uncovered intangible heterogeneity of gene effects in the survival time of patients.Research square · 2023Article
- c-Kit Receptors as a Therapeutic Target in Cancer: Current Insights.OncoTargets and therapy · 2023Review
Corrections and comments
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Authors and funding
8 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Expression profiling has identified four consensus molecular subtypes (CMS1-4) in colorectal cancer (CRC). The receptor tyrosine kinase KIT has been associated with the most aggressive subtype, CMS4. However, it is unclear whether, and how, KIT contributes to the aggressive features of CMS4 CRC. Here, we employed genome-editing technologies in patient-derived organoids (PDOs) to study KIT function in CRC in vitro and in vivo. CRISPR-Cas9-mediated deletion of the KIT gene caused a partial mesenchymal-to-epithelial phenotype switch and a strong reduction of intra-tumor stromal content. Vice versa, overexpression of KIT caused a partial epithelial-to-mesenchymal phenotype switch, a strong increase of intra-tumor stromal content, and high expression of TGFβ1. Surprisingly, the levels of phosphorylated SMAD2 were significantly lower in KIT-expressing versus KIT-deficient tumor cells. In vitro analyses showed that TGFβ signaling in PDOs limits their regenerative capacity. Overexpression of KIT prevented tumor-suppressive TGFβ signaling, while KIT deletion sensitized PDOs to TGFβ-mediated growth inhibition. Mechanistically, we found that KIT expression caused a strong reduction in the expression of SMAD2, a central mediator of canonical TGFβ signaling. We propose that KIT induces a pro-fibrotic tumor microenvironment by stimulating TGFβ expression, and protects the tumor cells from tumor-suppressive TGFβ signaling by inhibiting SMAD2 expression.
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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.