Copper enhances genotoxic drug resistance via ATOX1 activated DNA damage repair

Whole-Transcriptome Sequencing Analyses of Nuclear Antixoxidant-1 in Endothelial Cells: Role in Inflammation and Atherosclerosis

“…For example, we demonstrated that: Atox1 is predominantly localized at the nucleus in the endothelium of inflamed atherosclerotic aorta compared to control aorta [ 17 ]; Atox1 translocates from the cytosol to the nucleus in response to exogenous Cu to function as a Cu-dependent transcription factor for cyclin D1 to promote cell proliferation [ 25 ]; G-protein-coupled receptor agonist angiotensin II stimulates Atox1 nuclear translocation to promote transcription of ecSOD in vascular smooth muscle cells, which protects against oxidative stress in hypertension [ 29 ]; inflammatory cytokine TNFα rapidly stimulates nuclear translocation of Atox1 in Cu- and TRAF4-dependent manner to upregulate cytosolic NADPH oxidase organizer, p47phox in ECs, which promotes ROS-dependent inflammatory angiogenesis in vivo [ 16 , 17 , 31 ]; and nuclear translocation of Atox1 potentiates activin A-induced cell migration and colony formation in colon cancer [ 27 ]. Consistent with our findings, others have also reported nuclear Atox1 in various cancers [ 21 , 22 , 32 , 33 , 34 ]. Jin et al reported that ATOX1 binds to the promoter of mediator of DNA damage checkpoint 1, which enhances its transcriptional activity and tumor growth [ 33 ].…”

“…Consistent with our findings, others have also reported nuclear Atox1 in various cancers [ 21 , 22 , 32 , 33 , 34 ]. Jin et al reported that ATOX1 binds to the promoter of mediator of DNA damage checkpoint 1, which enhances its transcriptional activity and tumor growth [ 33 ]. Chen et al reported that APEX2-based proximity labeling of Atox1 identifies cysteine-rich protein 2 (CRIP2) as a nuclear Cu-binding protein that regulates autophagy activation in lung cancer H1299 cells [ 32 ].…”

Construction and systematic evaluation of a machine learning-based cuproptosis-related lncRNA score signature to predict the response to immunotherapy in hepatocellular carcinoma

“…Currently, studies have proven that the level of copper correlates with various biochemical processes. One published article pointed out that a high level of copper enhanced the drug resistance and was involved in DNA damage repair in cancer cells ( 33 ). One previous article demonstrated that copper accumulation reduced the proportion of cells in G2/M phase via Ras/PI3K/Akt signaling ( 34 ).…”

Cuproptosis-Mediated Patterns Characterized by Distinct Tumor Microenvironment and Predicted the Immunotherapy Response for Gastric Cancer

“…Under the normal physiological state, copper ions maintain a low concentration and dynamic balance in the organism, whereas the abnormal accumulation of copper ions can cause copper toxicity, and then induce cell death. , Studies have shown that mutations in human genes can lead to the imbalance of copper homeostasis and induce a variety of diseases, and its metabolic abnormalities can cause anemia, CCS syndrome, and congenital glycosylation disorders, as well as cancers. − It has been reported that copper imbalance promotes metastasis amplification through the OX-ATP7A-LOx pathway . In addition, several studies have found that copper ion carriers and their chelating agents are expected to be potential drug molecules for tumor therapy. − However, the molecular specific mechanism of the copper-mediated cell death remains unclarified.…”