Selected electrophile and drug detoxication genes down-regulated in A549 and H460 cells (lung cancer) upon knockdown of NFE2L2 [GeneID=4780] by RNAi.
| PAG Title | Selected electrophile and drug detoxication genes down-regulated in A549 and H460 cells (lung cancer) upon knockdown of NFE2L2 [GeneID=4780] by RNAi. |
| PAG ID | MAX002681 |
| Type | A |
| Source Link |  MSigDB |
| Publication Reference | NA |
| PAG Description | Nuclear factor erythroid-2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that regulates the expression of electrophile and xenobiotic detoxification enzymes and efflux proteins, which confer cytoprotection against oxidative stress and apoptosis in normal cells. Loss of function mutations in the Nrf2 inhibitor, Kelch-like ECH-associated protein (Keap1), results in constitutive activation of Nrf2 function in non-small cell lung cancer. In this study, we show that constitutive activation of Nrf2 in lung cancer cells promotes tumorigenicity and contributes to chemoresistance by up-regulation of glutathione, thioredoxin, and the drug efflux pathways involved in detoxification of electrophiles and broad spectrum of drugs. RNAi-mediated reduction of Nrf2 expression in lung cancer cells induces generation of reactive oxygen species, suppresses tumor growth, and results in increased sensitivity to chemotherapeutic drug-induced cell death in vitro and in vivo. Inhibiting Nrf2 expression using naked siRNA duplexes in combination with carboplatin significantly inhibits tumor growth in a subcutaneous model of lung cancer. Thus, targeting Nrf2 activity in lung cancers, particularly those with Keap1 mutations, could be a promising strategy to inhibit tumor growth and circumvent chemoresistance. |
| Species | Homo sapiens |
| nCoCo Score | 478 |
| Base PAG ID | MAX002681 |
| Human Phenotyte Annotation | |
| Curator | PAGER curation team |
| Curator Contact | PAGER-contact@googlegroups.com |
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