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10.1016/S0140-6736(12)61084-8 [DOI] [PubMed] [Google Scholar] 72

Bai J, Odin JA

PI3K inhibitor impairs AKT phosphorylation and synergizes with novel angiogenesis inhibitor AL3810 in human hepatocellular carcinoma

Several mechanisms have been reported for the increased activity of NRF2 in cancers ( Figure 5 ): (1) somatic mutations in KEAP1 or NRF2 , (2) DNA hypermethylation at the promoter region of KEAP1 , (3) the aberrant accumulation of proteins that disrupt the KEAP1NRF2 interaction, (4) transcriptional up-regulation of NRF2 gene through oncogene-dependent signaling, and (5) the modification of KEAP1 protein through oncometabolites