We previously demonstrated that the transcription factor @entity13791 ( @entity13791 ), expressed abundantly in @entity1149 ( @entity1149 ) cells, plays a pivotal role in the proliferation and chemoresistance of @entity1149 . Here we show that @entity13791 -mediated @entity1149 cell proliferation is dually regulated by @entity470 ( @entity470 ) signaling and an @entity13791 repressor protein @entity13792 ( @entity13792 ). @entity1149 cells expressing wild-type @entity470 and @entity13792 genes show enhanced proliferation on stimulation with @entity470 ligand under non-stress conditions. Exposure to @entity1981 ( @entity1981 ) enhanced cell proliferation by modification of the @entity13791 / @entity13792 interaction. Although @entity470 - @entity669 kinase inhibitor (TKI) inhibited the proliferation of these cells, exposure to @entity1981 attenuated its efficacy. In @entity1149 cells with @entity13792 gene mutations, @entity13791 was constitutively activated owing to dysfunction of @entity13792 and cells proliferated independently of @entity470 signaling. Furthermore, @entity470 was unable to inhibit their proliferation. In @entity1149 cells with @entity470 gene mutations, @entity13791 was constitutively activated by @entity470 signaling. In these cells, proliferation was largely dependent on the @entity470 signaling pathway. Although these cells were highly sensitive to @entity470 -TKI, exposure to @entity1981 or knockdown of @entity13792 mRNA reduced sensitivity to @entity470 . We found a case of @entity1149 showing resistance to @entity470 despite having @entity470 -TKI-sensitive @entity470 gene mutation because of dysfunctional mutation in @entity13792 gene. Results indicate that oxidative stress reduces the anticancer effects of @entity470 in wild-type @entity13792 @entity1149 cells. Analysis of @entity13792 dysfunction may become a novel molecular marker to predict resistance to @entity470 in @entity1149 cells having @entity470 -TKI-sensitive @entity470 mutations. Finally, as the downstream molecule of both @entity470 and @entity13792 signaling, @entity13791 is an important molecular target for the treatment of @entity1149 , where cells have mutations in @entity470 , @entity984 or @entity13792 genes.

Molecular mechanisms for the regulation of XXXX -mediated cell proliferation in @entity1149 .

@entity13792 :: ('9817', 'Gene') :: ['Keap1', 'Kelch-like ECH-associated protein-1'] @entity470 :: ('1956', 'Gene') :: ['EGFR-TKI', 'EGFR', 'epidermal growth factor receptor'] @entity984 :: ('3845', 'Gene') :: ['KRAS'] @entity1149 :: ('MESH:D002289', 'Disease') :: ['NSCLC', 'non-small-cell lung cancer'] @entity13791 :: ('4780', 'Gene') :: ['NF-E2-related factor2', 'Nrf2'] @entity669 :: ('CHEBI:18186', 'Chemical') :: ['tyrosine'] @entity1981 :: ('OMIM:188890', 'Disease') :: ['CSE', 'cigarette smoke extract']
@entity13791 :: (4780,Gene) :: ['Nrf2']
