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Dysfunctional KEAP1–NRF2 Interaction in Non-Small-Cell Lung Cancer

PLoS Medicine · 2006 · Vol. 3(10) · pp. e420–e420

Anju Singh(Johns Hopkins University)Vikas Misra(Johns Hopkins University)Rajesh K. Thimmulappa(Johns Hopkins University)Hannah Lee(Johns Hopkins University)Stephen Ames(Sidney Kimmel Comprehensive Cancer Center)Mohammad Obaidul Hoque(Johns Hopkins University)James G. Herman(Johns Hopkins University)Stephen B. Baylin(Johns Hopkins University)David Sidransky(Sidney Kimmel Comprehensive Cancer Center)Edward Gabrielson(Johns Hopkins University)Malcolm V. Brock(Johns Hopkins University)Shyam Biswal✉(Sidney Kimmel Comprehensive Cancer Center)

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Abstract

This is the first study to our knowledge to demonstrate that biallelic inactivation of KEAP1 is a frequent genetic alteration in NSCLC. Loss of KEAP1 function leading to constitutive activation of NRF2-mediated gene expression in cancer suggests that tumor cells manipulate the NRF2 pathway for their survival against chemotherapeutic agents.

Genomics, phytochemicals, and oxidative stress Nitrogen and Sulfur Effects on Brassica Glutathione Transferases and PolymorphismsKEAP1BiologyCancer researchLoss of heterozygosityMolecular biologyGeneticsTranscription factorGeneAllele

MeSH terms

Kelch-Like ECH-Associated Protein 1AdenocarcinomaAntineoplastic AgentsCarcinoma, Non-Small-Cell LungCarcinoma, Squamous CellHumansLung NeoplasmsMutationGene Expression Regulation, NeoplasticCarcinoma, Large CellDrug Resistance, NeoplasmCell Line, TumorIntracellular Signaling Peptides and ProteinsNF-E2-Related Factor 2