ArticleJournal of translational medicine2024
Wnt/β-catenin signalling activates IMPDH2-mediated purine metabolism to facilitate oxaliplatin resistance by inhibiting caspase-dependent apoptosis in colorectal cancer.
Article in Journal of translational medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 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
23 citing papers in PubMed.
- Metabolic immune checkpoints (MICs) in cancer: from molecular mechanisms to challenges and opportunities in clinical translation.Signal transduction and targeted therapy · 2026Review
- Volatilomic Signatures of Parental and Oxaliplatin-Resistant HCT116 Colon Cancer Cell Lines.International journal of molecular sciences · 2026Article
- Combined Analysis of Bulk and Single-Cell Transcriptomic Data Reveals Dormancy-Associated Genes in Colorectal Cancer.International journal of molecular sciences · 2026Article
- Downregulation of the host ribonucleotide reductase subunit M2 via the Wnt/β-catenin pathway is a novel mechanism for duck plague virus replication and a potential antiviral target.Poultry science · 2026Article
- Inflammation and Colorectal Cancer Pathogenesis: Molecular, Immunological, and Environmental Features for Therapy Response and Resistances.International journal of molecular sciences · 2026Review
- From Gut Homeostasis to Colorectal Cancer: Spatial and Temporal Reprogramming of Microbial Inosine Signaling.Biomedicines · 2026Review
- Expanding the targeted protein degradation approach with small molecule chimeras directed to the 26S proteasome.Nature communications · 2026Article
- Study of ß-catenin signaling pathway modulated by PTHrP in cell and animal colorectal cancer models.Frontiers in oncology · 2026Article
- AVN944 Elicits Apoptotic Responses and Impedes Tumorigenic Potential in Ewing's Sarcoma Cells.International journal of biological sciences · 2026Article
- BE screen reveals METTL3 S2 dephosphorylation sensitizes gastric cancer cells to oxaliplatin by interfering METTL3-eIF3H interaction.Science advances · 2025Article
- Article
- Distinctive chromosomal, mutational and transcriptional profiling in colon versus rectal cancers.Journal of translational medicine · 2025Article
- Glucose metabolism and its direct action in cancer and immune regulation: opportunities and challenges for metabolic targeting.Journal of biomedical science · 2025Review
- USP5 deubiquitinates and stabilizes IMPDH2, to promote hepatocellular carcinoma progression.Oncogene · 2025Article
- IMPDH2's Central Role in Cellular Growth and Diseases: A Potential Therapeutic Target.Cell proliferation · 2025Review
- Novel machine-learning bioinformatics reveal distinct metabolic alterations for enhanced colorectal cancer diagnosis and monitoring.iMetaOmics · 2025Article
- Article
- Wnt signaling pathways in biology and disease: mechanisms and therapeutic advances.Signal transduction and targeted therapy · 2025Review
- Inosine monophosphate dehydrogenase 2 (IMPDH2) modulates response to therapy and chemo-resistance in triple negative breast cancer.Scientific reports · 2025Article
- Elucidating the Mechanisms of Acquired Palbociclib Resistance via Comprehensive Metabolomics Profiling.Current issues in molecular biology · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
12 authors.
Funding
Abstract
backgroundOxaliplatin resistance usually leads to therapeutic failure and poor prognosis in colorectal cancer (CRC), while the underlying mechanisms are not yet fully understood. Metabolic reprogramming is strongly linked to drug resistance, however, the role and mechanism of metabolic reprogramming in oxaliplatin resistance remain unclear. Here, we aim to explore the functions and mechanisms of purine metabolism on the oxaliplatin-induced apoptosis of CRC.
methodsAn oxaliplatin-resistant CRC cell line was generated, and untargeted metabolomics analysis was conducted. The inosine 5'-monophosphate dehydrogenase type II (IMPDH2) expression in CRC cell lines was determined by quantitative real-time polymerase chain reaction (qPCR) and western blotting analysis. The effects of IMPDH2 overexpression, knockdown and pharmacological inhibition on oxaliplatin resistance in CRC were assessed by flow cytometry analysis of cell apoptosis in vivo and in vitro.
resultsMetabolic analysis revealed that the levels of purine metabolites, especially guanosine monophosphate (GMP), were markedly elevated in oxaliplatin-resistant CRC cells. The accumulation of purine metabolites mainly arose from the upregulation of IMPDH2 expression. Gene set enrichment analysis (GSEA) indicated high IMPDH2 expression in CRC correlates with PURINE_METABOLISM and MULTIPLE-DRUG-RESISTANCE pathways. CRC cells with higher IMPDH2 expression were more resistant to oxaliplatin-induced apoptosis. Overexpression of IMPDH2 in CRC cells resulted in reduced cell death upon treatment with oxaliplatin, whereas knockdown of IMPDH2 led to increased sensitivity to oxaliplatin through influencing the activation of the Caspase 7/8/9 and PARP1 proteins on cell apoptosis. Targeted inhibition of IMPDH2 by mycophenolic acid (MPA) or mycophenolate mofetil (MMF) enhanced cell apoptosis in vitro and decreased in vivo tumour burden when combined with oxaliplatin treatment. Mechanistically, the Wnt/β-catenin signalling was hyperactivated in oxaliplatin-resistant CRC cells, and a reciprocal positive regulatory mechanism existed between Wnt/β-catenin and IMPDH2. Blocking the Wnt/β-catenin pathway could resensitize resistant cells to oxaliplatin, which could be restored by the addition of GMP.
conclusionsIMPDH2 is a predictive biomarker and therapeutic target for oxaliplatin resistance in CRC.
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.