ArticleJournal of experimental & clinical cancer research : CR2019
The JAK2/STAT3/CCND2 Axis promotes colorectal Cancer stem cell persistence and radioresistance.
Article in Journal of experimental & clinical cancer research : CR, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 189 papers, 2 of them syntheses that pooled it.
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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.
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Who cites it
189 citing papers in PubMed, 2 syntheses or guidelines pooled it, 307 citations in OpenAlex.
- The Radiosensitizing Potentials of Silymarin/Silibinin in Cancer: A Systematic Review.Current medicinal chemistry · 2024Pooled it
- Bridging Radiotherapy to Immunotherapy: The IFN-JAK-STAT Axis.International journal of molecular sciences · 2021Pooled it
- Glucose-induced histone lactylation confers metformin resistance in colorectal cancer stem cells.Nature communications · 2026Article
- CCT2 Promotes Immune Escape in Colorectal Cancer by Regulating the JAK1-STAT3-PD-L1 Axis.Journal of gastroenterology and hepatology · 2026Article
- Cancer Stem Cells in Colorectal Cancer: From Molecular Mechanisms to Diagnosis, Prognosis and Therapy Implications.Cancers · 2026Review
- Microbiome-Shaped Metastatic Niches in Colorectal Cancer: Organ-Specific Patterns, Immune-Metabolic Mechanisms, and Therapeutic Translation.Microorganisms · 2026Review
- The STAT3-CCND2 Axis Drives a Proliferative Metaplastic Precursor Population in Gastric Intestinal Metaplasia.Journal of cellular and molecular medicine · 2026Article
- JAK-STAT signaling pathway in cancer: from molecular mechanisms to clinical intervention.Molecular cancer · 2026Review
- Multi-omics analysis of patient-derived organoids reveals that E3 ligase COP1 promotes liver metastasis and oxaliplatin resistance in colorectal cancer through LUZP1 degradation and MYL9 phosphorylation.Experimental hematology & oncology · 2026Article
- A 13-gene prognostic model developed using machine learning to predict the response to neoadjuvant chemoradiotherapy in rectal carcinoma.Cancer cell international · 2026Article
- Nitroxoline Enhances Radiosensitivity in Non-Small Cell Lung Cancer by Suppressing STAT3-AKT-MTOR Survival Signaling.International journal of molecular sciences · 2026Article
- Cancer stem cell-driven drug resistance in colorectal carcinoma: molecular aspects and therapeutic potentials.Molecular cancer · 2026Review
- ACYP2 Induces Temozolomide Resistance in Glioblastoma by Promoting PARP1-Mediated DNA Damage Repair.Molecular cancer research : MCR · 2026Article
- MicroRNA-661 Suppresses Proliferation and Migration of Pulmonary Artery Smooth Muscle Cells and Endothelial Cells by Targeting CCND2.Biologics : targets & therapy · 2026Article
- FOXP1-transcriptionally regulated AEG-1 enhances tumor cell stemness to promote hepatocellular carcinoma radioresistance.Molecular and cellular biochemistry · 2026Article
- Article
- Regorafenib-Induced Stress Response Alters the Bioenergetic Profile of Osteosarcoma Cells and Modulates Gene Expression Associated with Metabolic regulation-a Potential Mechanism of Osteosarcoma Treatment-Related Adaptation.Cancer management and research · 2026Article
- Glutamine metabolism and its roles in tumor radiotherapy by regulating DNA damage repair.Frontiers in cell and developmental biology · 2026Review
- Review
- Cancer-associated fibroblast-induced lncRNA WARS2-IT1 confers radioresistance of colorectal cancer via enhancing HIF-1α stability.Cell death & disease · 2025Article
129 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
Abstract
backgroundRadiotherapy (RT) is a highly effective multimodal nonsurgical treatment that is essential for patients with advanced colorectal cancer (CRC). Nevertheless, cell subpopulations displaying intrinsic radioresistance survive after RT. The reactivation of their proliferation and successful colonization at local or distant sites may increase the risk of poor clinical outcomes. Recently, radioresistant cancer cells surviving RT were reported to exhibit a more aggressive phenotype than parental cells, although the underlying mechanisms remain unclear.
methodsBy investigating public databases containing CRC patient data, we explored potential radioresistance-associated signaling pathways. Then, their mechanistic roles in radioresistance were investigated through multiple validation steps using patient-derived primary CRC cells, human CRC cell lines, and CRC xenografts.
resultsJanus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling was activated in radioresistant CRC tissues in correlation with local and distant metastases. JAK2 was preferentially overexpressed in the CRC stem cell subpopulation, which was accompanied by the phosphorylation of STAT proteins, especially STAT3. JAK2/STAT3 signaling played an essential role in promoting tumor initiation and radioresistance by limiting apoptosis and enhancing clonogenic potential. Mechanistically, the direct binding of STAT3 to the cyclin D2 (CCND2) promoter increased CCND2 transcription. CCND2 expression was required for persistent cancer stem cell (CSC) growth via the maintenance of an intact cell cycle and proliferation with low levels of DNA damage accumulation.
conclusionHerein, we first identified JAK2/STAT3/CCND2 signaling as a resistance mechanism for the persistent growth of CSCs after RT, suggesting potential biomarkers and regimens for improving outcomes among CRC patients.
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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.