To clarify metabolic features of NRF2-activated lung cancers, we conducted targeted metabolomic (T-Met) and global metabolomic (G-Met) analyses of non-small-cell lung cancer (NSCLC) cell lines in combination with exome and transcriptome analyses.
Finally, we report that NRF2 protein expression in a NSCLC cohort exceeds the typical incidence of combined NRF2, KEAP1, and CUL3 mutations, and that NRF2 expression in this cohort is correlated with PIDD levels.
Taken together, our results indicate that the Nestin-Keap1-Nrf2 axis regulates cellular redox homeostasis and confers oxidative stress resistance in NSCLC.
In non-small cell lung cancer (NSCLC) cells and xenografts, MKP-1 knockdown triggered the down-regulation of the metabolic enzymes and cytoprotective proteins, which are the target genes of Nrf2.
Using multiple isogenic non-small cell lung cancer (NSCLC) cell lines, we observed a reduction of Nrf2 protein and activity in a prometastatic mesenchymal cell state and increased reactive oxygen species.
This study demonstrates that the NRF2 pathway may serve as a therapeutic target in NSCLC, and ginseng compounds may be effective for the treatment of this disease.
SIGNIFICANCE: This study identifies pathways activated by Nrf2 that are important for the proliferation and tumorigenicity of KEAP1-mutant non-small cell lung cancer.
In the present study a traditional Chinese medicine, triptolide, was identified that markedly inhibited expression and transcriptional activity of Nrf2 in various cancer cells, including NSCLC and liver cancer cells.
In this study, we discovered that overexpression of antioxidant-responsive element (ARE)-containing Nrf2 target genes by increased transactivation of Nrf2 occurred because of an acquired Keap1 mutation in the gefitinib-resistant (GR) NSCLC cell line we established.
The transcription factor NRF2 is a master regulator of the cellular antioxidant response, and it is often genetically activated in non-small-cell lung cancers (NSCLCs) by, for instance, mutations in the negative regulator KEAP1.
Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway.
Non-small cell lung cancer (NSCLC) cells often possess a hypermethylated Keap1 promoter, which decreases Keap1 mRNA and protein expression levels, thus impairing the Nrf2-Keap1 pathway and thereby leading to chemo- or radio-resistance.
Nrf2 is often constitutively activated in non-small cell lung cancer (NSCLC) cell lines, which promotes cytoprotection against oxidative stress and xenobiotics.
Our findings suggest that NRF2 signaling plays an indispensable role in NSCLC cell sensitivity to platinum-based treatments and provides a rationale for using NRF2 as a specific biomarker for predicting which patients will be most likely to benefit from platinum-based treatment.