ArticleOncogene2025
CBX3 promotes multidrug resistance by suppressing ferroptosis in colorectal carcinoma via the CUL3/NRF2/GPX2 axis.
Article in Oncogene, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed.
- PUM2 inhibits ferroptosis and enhances oxaliplatin resistance in COAD via the NEDD4L/NRF2 axis.Translational oncology · 2026Article
- Mechanisms and advances of drug resistance in colorectal cancer: A systematic overview of multi-layered regulatory networks.Translational oncology · 2026Review
- Histone Post-Translational Modifications Regulating Ferroptosis: The Molecular Mechanisms and Disease Associations.Cell biochemistry and function · 2026Review
- P53 Competitively Binds P300 to Suppress HIF-1α/TFRC-Mediated Ferroptosis and Promote Doxorubicin Resistance in Breast Cancer.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2026Article
- Cancer drug response and resistance: molecular mechanisms and combating strategies.Signal transduction and targeted therapy · 2026Review
- Review
- Selenoproteins: Minute yet vital players governing cellular fate.Genes & diseases · 2026Review
- USP10 confers lenvatinib resistance in hepatocellular carcinoma by deubiquitinating the GPX2.Cellular oncology (Dordrecht, Netherlands) · 2026Article
- Nanomagnetic Hyperthermia Sensitizes Gemcitabine Chemosensitivity in Pancreatic Cancer by Inhibiting HSPB1 to Amplify ACSL4-Mediated Ferroptosis.Small (Weinheim an der Bergstrasse, Germany) · 2026Article
- CBX3:IL1RN Reflects Distinct Cellular States That Defines the Clinical Outcome of Oral Squamous Cell Carcinoma.Cancer medicine · 2026Article
- Ferroptosis: The dawn of reversing drug resistance in digestive cancers.Genes & diseases · 2026Review
- Ferroptosis and metastasis: molecular checkpoints, microenvironmental dynamics, and therapeutic opportunities.Molecular cancer · 2026Review
- Autophagy regulation of pyroptosis and ferroptosis: a new strategy for colorectal cancer treatment.Apoptosis : an international journal on programmed cell death · 2026Review
- Natural products targeting the Nrf2 signaling pathway: potential targets and intervention strategies for the prevention and treatment of colorectal cancer.Frontiers in pharmacology · 2026Review
- Research advances in single-molecule multi-target strategies targeting ferroptosis for colorectal cancer treatment.American journal of cancer research · 2026Review
- GPX2+ tumor cells recruit LGALS1+ B cells via CCL26-CCR3 axis to promote immunosuppression and tumor progression in hepatocellular carcinoma.Frontiers in immunology · 2026Article
- CBX3 promotes epithelial-mesenchymal transition in synovial sarcoma via the SHH signaling pathway.American journal of cancer research · 2026Article
- Analysis of cullin family genes in rectal adenocarcinoma: expression, prognostic significance, and therapeutic implications.American journal of translational research · 2025Article
- Shikonin improves intestinal barrier function through modulation of GPX4 expression in intestinal epithelial cells.International journal of immunopathology and pharmacologyArticle
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Authors and funding
14 authors.
Funding
Abstract
Chemoresistance poses a significant challenge in colorectal cancer (CRC) treatment. However, the mechanisms underlying chemoresistance remain unclear. CBX3 promoted proliferation and metastasis in CRC. However, the role and mechanism of CBX3 in chemoresistance remain unknown. Therefore, we aimed to investigate the effects and mechanisms of CBX3 on multidrug resistance in CRC. Our studies showed that higher levels of CBX3 expression were associated with poor survival, especially in groups with progression following chemotherapy. CBX3 overexpression increased Irinotecan and Oxaliplatin resistance, whereas CBX3 knockdown suppressed multidrug resistance in CRC cells. Additionally, CBX3 inhibited ferroptosis associated with multidrug resistance, and the ferroptosis activators prevented CBX3 overexpression-mediated cell survival. RNA sequencing revealed that the NRF2-signaling pathway was involved in this process. CBX3-upregulated NRF2 protein expression by directly binding to the promoter of Cullin3 (CUL3) to suppress CUL3 transcription and CUL3-mediated NRF2 degradation. Moreover, Glutathione Peroxidase 2 (GPX2) was downstream of the CBX3-NRF2 pathway in CRC chemoresistance. ML385, an NRF2 inhibitor, suppressed GPX2 expression, and increased ferroptosis in PDX models. Our study identified CBX3/NRF2/GPX2 axis may be a novel signaling pathway that mediates multidrug resistance in CRC. This study proposes developing novel strategies for cancer treatment to overcome drug resistance in the future.
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