ArticleSignal transduction and targeted therapy2022
Single-cell transcriptomic profiling unravels the adenoma-initiation role of protein tyrosine kinases during colorectal tumorigenesis.
Article in Signal transduction and targeted therapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers.
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64 citing papers in PubMed, 109 citations in OpenAlex.
- Integrated single-cell and spatial transcriptomic analyses reveal malignant epithelial glycolytic heterogeneity and spatial niche remodeling during colorectal cancer progression.Functional & integrative genomics · 2026Article
- The Single-Cell and Spatial Transcriptomics Atlas of Epithelial-Fibroblast Interactions in Colorectal Cancer.Digestive diseases and sciences · 2026Article
- Single-cell transcriptomics and functional analyses identified SPIN.DOC as a regulator for Wnt signaling and cancer stemness in colorectal cancer.Human cell · 2026Article
- GALNT5 drives colorectal cancer progression and chemoresistance via PI3K/Akt/ABCC1 axis.Journal of cancer research and clinical oncology · 2026Article
- CLEC2B-KLRB1 axis acts as an immune checkpoint, governing the exhaustion of CD8Journal for immunotherapy of cancer · 2026Article
- Subcellular Redistribution of Endomembrane GPR15 Promotes NAD+-Mediated Metabolic Reprogramming and Boosts 5-FU Chemosensitivity in Colorectal Cancer.Cancer research · 2026Article
- SNHG7 interacts with PCBP2 to promote CDKN2A expression and modulate cuproptosis in colorectal cancer.Translational oncology · 2026Article
- A Soft Matrix Microenvironment Promotes Laterally Spreading Tumors via Oxidative Phosphorylation-Dependent Cell Adhesion.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- RUNX2 drives adenoma-to-carcinoma transition in colon cancer.Cell death & disease · 2026Article
- A multimodal approach integrating NK cell-associated gene signatures and pathomics to predict colon adenocarcinoma prognosis.Scientific reports · 2026Article
- A hybrid molecular-imaging model for high-accuracy early colorectal cancer diagnosis.Journal of gastrointestinal oncology · 2026Article
- Amelioration of colorectal cancer-associated fibroblasts in immunosuppressive microenvironment by ferroptosis-based nanotherapy.Nature communications · 2026Article
- Hsa-miR-99a deficiency contributes to MSI-H colorectal cancer progression by activating the mTOR pathway and inducing Th1/Th2 imbalance.Frontiers in immunology · 2026Article
- Bioinformatics combined with machine learning for the identification of malignant transformation markers in colorectal polyps.Frontiers in molecular biosciences · 2026Article
- Single-cell and spatial transcriptome profiling identifies the immunosuppressive spatial niche inJournal for immunotherapy of cancer · 2025Article
- Atorvastatin suppresses high-risk colorectal adenomas via reprogramming of lipid metabolism and Inhibition of stemness.Scientific reports · 2025Article
- Targeting the CD47-HCK-LGALS9 axis disrupts proliferation-immunosuppression coupling in early-stage endometrial cancer.Molecular cancer · 2025Article
- Article
- Deciphering Ferroptosis-Related Astrocyte Subpopulations and Diagnostic Biomarkers in Parkinson's Disease through RNA Transcriptomics.Molecular neurobiology · 2025Article
- Plasma metabolites, metabolic risk score and colorectal cancer risk: a prospective cohort study.European journal of epidemiology · 2025Article
4 more citing papers are in PubMed but not listed here.
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20 authors at 4 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The adenoma-carcinoma sequence is a well-accepted roadmap for the development of sporadic colorectal cancer. However, cellular heterogeneity in aberrant epithelial cells limits our understanding of carcinogenesis in colorectal tissues. Here, we performed a single-cell RNA sequencing survey of 54,788 cells from patient-matched tissue samples, including blood, normal tissue, para-cancer, polyp, and colorectal cancer. At each stage of carcinogenesis, we characterized cell types, transcriptional signatures, and differentially expressed genes of distinct cell populations. The molecular signatures of epithelial cells at normal, benign, and malignant stages were defined at the single-cell scale. Adenoma and carcinoma precursor cell populations were identified and characterized followed by validation with large cohort biopsies. Protein tyrosine kinases (PTKs) BMX and HCK were identified as potential drivers of adenoma initiation. Specific BMX and HCK upregulations were observed in adenoma precursor cell populations from normal and adenoma biopsies. Overexpression of BMX and HCK significantly promoted colorectal epithelial cell proliferation. Importantly, in the organoid culture system, BMX and HCK upregulations resulted in the formation of multilayered polyp-like buds protruding towards the organoid lumen, mimicking the pathological polyp morphology often observed in colorectal cancer. Molecular mechanism analysis revealed that upregulation of BMX or HCK activated the JAK-STAT pathway. In conclusion, our work improved the current knowledge regarding colorectal epithelial evolution during carcinogenesis at the single-cell resolution. These findings may lead to improvements in colorectal cancer diagnosis and treatment.
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